Uzoq kodlamaydigan RNK - Long non-coding RNA

Uzoq kodlamaydigan RNKlar (uzun ncRNAlar, lncRNA) turlari RNK, bo'lish deb ta'riflangan stenogrammalar uzunligi 200 dan oshiq nukleotidlar oqsilga tarjima qilinmagan.[1] Bu o'zboshimchalik bilan cheklangan uzun ncRNA ni mayda-chuydan ajratib turadi kodlamaydigan RNKlar kabi mikroRNKlar (miRNA), kichik aralashuvchi RNKlar (siRNA), Pivi bilan o'zaro ta'sir qiluvchi RNKlar (piRNAlar), kichik nukleolyar RNKlar (snoRNAlar) va boshqa qisqa RNKlar.[2] Uzoq vaqt oralig'idagi / intergenik kodlamaydigan RNKlar (lincRNAs) - bu lncRNA ning ketma-ketligi bo'lib, ular oqsillarni kodlovchi genlar bilan bir-birining ustiga chiqmaydi.[3]

Mo'llik

2007 yilda o'tkazilgan tadqiqotlar shundan faqat beshdan bir qismini topdi transkripsiya bo'ylab inson genomi oqsillarni kodlovchi genlar bilan bog'liq,[4] kodlashning RNK ketma-ketliklaridan kamida to'rt baravar ko'pligini ko'rsatib turibdi. Biroq, bu keng ko'lamli bir-birini to'ldiruvchi DNK (cDNA) kabi loyihalarni tartiblashtirish FANTOM Ushbu transkripsiyaning murakkabligini ochadigan (sutemizuvchilarning cDNA-ning funktsional izohi).[5] FANTOM3 loyihasi mRNKlarning ko'plab imzolarini o'z ichiga olgan ~ 10000 ta aniq lokuslardan ~ 35000 ta kodlamaydigan transkriptlarni, shu jumladan 5'ni yopish, birlashtirish va poli-adenilatsiyani aniqladi, ammo kam yoki umuman yo'q. ochiq o'qish doirasi (ORF).[5] Uzoq ncRNAlarning ko'pligi kutilmagan bo'lsa-da, bu raqam konservativ past bahoni anglatadi, chunki u ko'plab singleton transkriptlari va boshqa bo'lmaganpoliadenillangan transkriptlar (plitka qatori ma'lumotlarga ko'ra transkriptlarning 40% dan ortig'i poliadenilatsiz).[6] Shu bilan birga, ushbu cDNA kutubxonalarida ncRNA-larni aniq aniqlash juda qiyin, chunki oqsillarni kodlash transkriptlarini kodlamaydigan transkriptlardan ajratish qiyin bo'lishi mumkin. Ko'plab tadqiqotlar orqali taklif qilingan moyak,[7] va asab to'qimalari har qanday kodlamaydigan uzoq RNKlarning eng katta miqdorini ifoda eting to'qima turi.[8] FANTOM5 yordamida insonning turli manbalarida 27919 uzun ncRNA aniqlandi.[9]

Son jihatdan lncRNA'lar hujayralar populyatsiyasida mRNKlarga qaraganda ~ 10 baravar past bo'lganligini ko'rsatadi,[10][11] oqsillarni kodlovchi genlar bilan taqqoslaganda, bu hujayralardagi lncRNA genlarining ekspression darajalarining hujayradan hujayraga yuqori o'zgarishi bilan izohlanadi.[12] Umuman olganda, lncRNKlarning aksariyati (~ 78%) mRNKlarning atigi ~ 19% dan farqli o'laroq, to'qimalarga xosdir.[10] LncRNAlar yuqori to'qimalarning o'ziga xos xususiyati bilan bir qatorda yuqori rivojlanish bosqichining o'ziga xos xususiyati bilan ajralib turadi,[13] va insonning neokorteks kabi heterojen to'qimalarda hujayra subtipining o'ziga xos xususiyati.[14] 2018 yilda lncRNAlarning mavjud ma'lumotlar bazalaridan, nashr etilgan adabiyotlardan va RNK-seq ma'lumotlarini tahlil qilish asosida yangi RNK-assambleyalardan har tomonlama integratsiyalashuvi natijasida odamlarda 270,044 lncRNA transkriptlari borligi aniqlandi.[15]

Sutemizuvchi hayvonlar bilan taqqoslaganda, ozgina tadqiqotlar o'simliklarda lncRNAlarning tarqalishiga qaratilgan. Ammo 37 ta yuqori o'simlik turlari va oltita suv o'tlarini hisobga olgan holda olib borilgan keng qamrovli tadqiqot an kodi yordamida ~ 200,000 kodlamaydigan transkriptlarni aniqladi silika yaqinlashish,[16] shu bilan birga Yashil kodlamaydigan ma'lumotlar bazasini yaratdi (GreeNC ), o'simlik lncRNAs ombori.

Genomik tashkilot

2005 yilda sutemizuvchilar genomining landshafti transkripsiyaning ko'p sonli "o'choqlari" sifatida tavsiflangan bo'lib, ular uzoq cho'zilib ketgan intergenik bo'sh joy.[5] Uzoq ncRNAlar intergenik cho'zilishlar oralig'ida joylashgan va transkripsiyalangan bo'lsa, aksariyati bir-birining ustiga chiqadigan murakkab, interlaced tarmoqlari sifatida yoziladi. sezgi va antisensiya ko'pincha proteinlarni kodlovchi genlarni o'z ichiga olgan transkriptlar,[4] bir-birining ustiga chiqib ketadigan izoformalarning murakkab iyerarxiyasini keltirib chiqaradi.[17] Ushbu transkripsiya markazidagi genomik ketma-ketliklar ko'pincha turli xil kodlash va kodlashsiz transkriptlarda ma'no va antisens yo'nalishlarda bo'lishadi.[18] Masalan, ilgari FANTOM2 ichidagi qisqartirilgan kodlash ketma-ketligi sifatida izoh berilgan 8961 cDNA-dan 3012 tasi keyinchalik kodlangan cDNA-larning asl ncRNA variantlari sifatida belgilandi.[5] Ushbu qatlamlarning ko'pligi va saqlanib qolishi ularning biologik ahamiyatga ega ekanligini ko'rsatsa-da, bu fokuslarning murakkabligi oson baholashga xalaqit beradi.

The JENKOD konsortsium inson lncRNA izohlari va ularning genomik tashkiloti, modifikatsiyalari, uyali joylashuvi va to'qimalarning ekspression profillarining keng qamrovli to'plamini birlashtirdi va tahlil qildi.[8] Ularning tahlillari shuni ko'rsatadiki, inson lncRNA-lari ikki ekzonli transkriptlarga moyil emas.[8]

Uzoq kodlamaydigan RNK identifikatsiyalash vositalari

IsmTurlarVeb-serverOmborFaylni kiritishAsosiy model / algoritmMashg'ulotlar to'plamiNashr qilingan yilMalumot
RNAsambaHammasiRNAsambaRNAsambaFASTANeyron tarmoqlariHA2020[19]
LGCO'simlik / hayvonLGCFASTA / BED / GTFORF uzunligi va GC tarkibi o'rtasidagi munosabatlarYOQ2019[20]
CPATInson / Fly / Sichqoncha / ZebrafishCPATCPATFASTA / yotoqLogistik regressiyaHA2013[21]
KELINGO'simlik / Inson / Sichqoncha / Fly / WormKELINGKELINGGTFBalansli tasodifiy o'rmonHA2017[22]
lncRScan-SVMInsonNAFASTA / BED / GTF / GFFVektorli mashinani qo'llab-quvvatlashHA2015[23]
CNCIO'simlik / hayvonNAFASTA / GTFVektorli mashinani qo'llab-quvvatlashYOQ2013[24]
PLEKUmurtqali hayvonlarNAPLEKFASTAVektorli mashinani qo'llab-quvvatlashYOQ2014[24]
FEELncHammasiNAFEELncFASTA / GTFTasodifiy o'rmonHA2017[25]
PhyloCSFOmurgalılar / Fly / Mosquito / Xamirturush / WormNAFASTAFilogenetik kodon modeliHA2011[26]
PLITO'simlikNAFASTALASSO / Tasodifiy o'rmonHA2018[27]
RNAploncO'simlikNAFASTAREPTreeHA2018[28]
PLncPROO'simlik / hayvonNAFASTATasodifiy o'rmonHA2017[29]
CREMAO'simlik / hayvonNAFASTAAnsamblga yaqinlashishHA2018[30]
jasurHammasiNAjasurFASTA / yotoqEvolyutsion konservatsiyaHA2016[31]

Tarjima

LncRNAlarning noto'g'ri izohlanganligi va aslida oqsillarni kodlashi haqida juda ko'p munozaralar mavjud. Aslida biologik ahamiyatga ega bo'lgan peptidlar uchun bir nechta lncRNA ning kodlanishi aniqlandi.[32][33][34] Ribozomalarni profillash bo'yicha tadqiqotlar shuni ko'rsatdiki, izohlangan lncRNAlarning 40% dan 90% gacha bo'lgan joylari aslida tarjima qilingan,[35][36] ribosoma profil ma'lumotlarini tahlil qilishning to'g'ri usuli haqida kelishmovchiliklar mavjud bo'lsa-da.[37] Bundan tashqari, lncRNAs tomonidan ishlab chiqarilgan peptidlarning ko'pi juda beqaror va biologik funktsiyasiz bo'lishi mumkin deb o'ylashadi.[36]

Tabiatni muhofaza qilish

LncRNA-ni saqlash bo'yicha dastlabki tadqiqotlar shuni ta'kidladiki, ular sinf sifatida konservalangan ketma-ketlik elementlari uchun boyitilgan,[38] almashtirish va qo'shish / o'chirish stavkalarida tükenmiştir[39] va kamdan-kam uchraydigan chastotali variantlarda,[40] lncRNA funktsiyasini qo'llab-quvvatlaydigan tozalash tanlovining ko'rsatkichi. Shu bilan birga, umurtqali lncRNA-lar bo'yicha keyingi tekshiruvlar natijasida lncRNA-lar ketma-ket saqlanib qolgan bo'lsa-da, ular transkripsiyada saqlanib qolmasligi aniqlandi.[41][42][7] Boshqacha qilib aytganda, boshqa lncRNA ketma-ketligi boshqa umurtqali hayvon turida saqlanib qolgan taqdirda ham, ko'pincha lncRNA ning transkripsiyasi bo'lmaydi. ortologik genomik mintaqa. Ba'zilar ushbu kuzatuvlar lncRNAlarning ko'pchiligining ishlamasligini taklif qiladi, deb ta'kidlaydilar,[43][44][45] boshqalar esa ularning tez turlarga xos adaptiv seleksiyani ko'rsatishi mumkin, deb ta'kidlaydilar.[46]

LncRNA transkripsiyasining aylanishi kutilganidan ancha yuqori bo'lsa-da, shuni ta'kidlash kerakki, hali ham yuzlab lncRNAlar ketma-ketlik darajasida saqlanib qoladi. LncRNAlar orasida ko'rilgan seleksiya imzolarining turli toifalarini ajratib olishga bir necha bor urinishlar bo'lgan, jumladan: genning butun uzunligi bo'ylab ketma-ketligi kuchli saqlanadigan lncRNAs, transkriptning faqat bir qismi bo'lgan lncRNAs (masalan, 5 "tugaydi, qo'shilish saytlari ) saqlanib qoladi va transkripsiyalangan lncRNAlar sintenik genomning mintaqalari, ammo taniqli ketma-ket o'xshashligi yo'q.[47][48][49] Bundan tashqari, lncRNA-larda saqlanib qolgan ikkilamchi tuzilmalarni aniqlashga urinishlar bo'lgan, ammo bu tadqiqotlar hozirda qarama-qarshi natijalarga yo'l ochib bergan.[50][51]

Vazifalar

Keng ko'lamli ketma-ketlik cDNA kutubxonalari va yaqinda transkriptomik tartiblash keyingi avlod ketma-ketligi uzun bo'lmagan kodlash RNKlari sutemizuvchilarda o'n minglab tartibda ekanligini ko'rsatadi. Biroq, ularning aksariyati funktsional bo'lishi mumkinligini ko'rsatadigan dalillarni to'plashga qaramay,[52][53] faqat nisbatan kichik qismi biologik ahamiyatga ega ekanligi isbotlangan. 2016 yil yanvar holatiga ko'ra 294 LncRNK funktsional izohlangan LncRNAdb (LncRNAlar tavsiflangan adabiyotlar bazasi),[54][55] ularning aksariyati (183 LncRNA) odamlarda tasvirlangan. 2018 yil iyun holatiga ko'ra, LncRNAWiki (inson lncRNA-larini jamoat kuratsiyasi uchun viki-ga asoslangan, ommaviy tahrirlanadigan va ochiq tarkibli platforma) da eksperimental dalillarga ega bo'lgan jami 1867 ta inson lncRNA-lari jamoatchilik tomonidan kurilgan.[56] funktsional mexanizmlar va kasallik assotsiatsiyalariga nisbatan, ularga kirish mumkin LncBook.[15] LncRNAlarning adabiyotlarga asoslangan funktsional mexanizmlarini kuratsiyasiga ko'ra, lncRNAs transkripsiyani boshqarishda ishtirok etishi haqida keng ma'lumot berilgan.[15] Keyinchalik keng ko'lamli ketma-ketlik bo'yicha tadqiqotlar, lncRNAlar deb hisoblangan ko'plab transkriptlarning, aslida, oqsillarga tarjima qilinishi mumkinligini isbotlaydi.[57]

Genlarning transkripsiyasini boshqarishda

Genga xos transkripsiyada

Eukaryotlarda RNK transkripsiyasi qat'iy tartibga solingan jarayondir. NcRNKlar ushbu jarayonning turli jihatlarini, transkripsiya faollashtiruvchilarini yoki repressorlarini, transkriptsiya reaktsiyasining turli tarkibiy qismlarini, shu jumladan yo'naltirishi mumkin RNK polimeraza (RNAP) II va hatto gen transkripsiyasini va ekspressionini tartibga solish uchun DNK dupleksi.[58] Birgalikda ushbu ncRNAlar tartibga soluvchi tarmoqni o'z ichiga olishi mumkin, bu transkripsiya omillarini o'z ichiga oladi, murakkab eukaryotlarda gen ekspressionini yaxshi boshqaradi.

NcRNAlar transkripsiya omillari funktsiyasini bir nechta turli xil mexanizmlar bilan modulyatsiya qiladi, shu jumladan o'zlarini koordinator sifatida ishlash, transkripsiya omilining faolligini o'zgartirish yoki koordinatorlarning assotsiatsiyasi va faoliyatini tartibga solish. Masalan, ncRNA Evf-2 homeobox transkripsiyasi faktori uchun birgalikda faollashtiruvchi vazifasini bajaradi Dxx2 oldingi miya rivojlanishi va neyrogenezida muhim rol o'ynaydi.[59][60] Sonic tipratikan Evf-2 ning transkripsiyasini an ultra saqlanib qolgan element o'rtasida joylashgan Dlx5 va Dlx6 oldingi miya rivojlanishi paytida genlar.[59] Evf-2 keyinchalik Dlx2 transkripsiya faktorini xuddi shu ultra saqlangan elementga jalb qiladi, shu bilan Dlx2 keyinchalik Dlx5 ekspressionini keltirib chiqaradi. Sutemizuvchilar genomida transkripsiyalangan va kuchaytiruvchi funktsiyalarni bajaradigan boshqa shunga o'xshash ultra yoki juda konservalangan elementlarning mavjudligi Evf-2 umurtqali hayvonlar o'sishi paytida murakkab ekspression naqshlari bilan muhim rivojlanish genlarini qat'iy tartibga soluvchi umumlashtirilgan mexanizmning tasviri bo'lishi mumkin.[61][62] Darhaqiqat, shunga o'xshash kodlamaydigan ultrakonservlangan elementlarning transkripsiyasi va ekspressioni odam leykemiyasida g'ayritabiiy ekanligi va yo'g'on ichak saraton hujayralarida apoptozga hissa qo'shishi, ularning shish paydo bo'lishida ishtirok etishini ko'rsatdi.[63][64]

Mahalliy ncRNAlar, qo'shni oqsillarni kodlovchi gen ekspressionini tartibga solish uchun transkripsiyaviy dasturlarni jalb qilishlari mumkin. Masalan, yaqin oqsillarni kodlovchi genlarga teskari yo'nalishda transkripsiya qilingan divergent lncRNAlar (sutemizuvchilar genomidagi umumiy lncRNAlarning ~ 20% ni tashkil qiladi), ehtimol pluripotent hujayralardagi yaqin qo'shni muhim rivojlanish regulyator genlarining transkripsiyasini tartibga soladi.[65]

RNK bilan bog'langan oqsil TLS, bog'laydi va inhibe qiladi CREB biriktiruvchi oqsil va p300 repressiya qilingan gen nishonidagi giston atsetiltransferaza faoliyati, siklin D1. TL1ni siklin D1 promouteriga jalb qilish past darajalarda ifodalangan va DNKning zararlanish signallariga javoban 5 'tartibga soluvchi hududlarga bog'langan uzun ncRNAlar tomonidan boshqariladi.[66] Bundan tashqari, ushbu mahalliy ncRNAlar TLS faoliyatini modulyatsiya qilish uchun ligandlar sifatida hamkorlik qiladi. Keng ma'noda, ushbu mexanizm hujayraga sutemizuvchi sut bezlari proteomidagi eng katta sinflardan birini tashkil etadigan RNK bilan bog'langan oqsillarni ishlatishga va ularning funktsiyalarini transkripsiya dasturlarida birlashtirishga imkon beradi. Yaratilgan uzun ncRNKlarning CREB bilan bog'langan oqsilning faolligini oshirishi isbotlangan, bu esa o'z navbatida ushbu ncRNA ning transkripsiyasini oshiradi.[67] Yaqinda o'tkazilgan bir tadqiqot shuni ko'rsatdiki, Apolipoprotein A1 (APOA1) ning antisens yo'nalishidagi lncRNA APOA1 transkripsiyasini epigenetik modifikatsiyalar orqali tartibga soladi.[68]

So'nggi ma'lumotlarga ko'ra, X-inaktivatsiyadan qochib qutuladigan genlarning transkripsiyasi qochib ketadigan xromosoma domenlari ichida uzoq vaqt kodlanmagan RNK ekspresiyasi orqali amalga oshirilishi mumkin.[69]

Bazal transkripsiya mexanizmlarini tartibga solish

NcRNAs shuningdek, uchun zarur bo'lgan umumiy transkripsiya omillarini maqsad qilib qo'ygan RNAP II barcha genlarning transkripsiyasi.[58] Ushbu umumiy omillar tarkibiga promotorlarda yig'iladigan yoki transkripsiya cho'zilishida ishtirok etadigan boshlang'ich kompleksining tarkibiy qismlari kiradi. NcRNK ning yuqoridagi kichik promotoridan transkripsiyasi dihidrofolat reduktaza (DHFR) geni transkripsiyaviy ko-faktorning bog'lanishiga yo'l qo'ymaslik uchun DHFR-ning asosiy promotorida barqaror RNK-DNK tripleksini hosil qiladi. TFIIB.[70] Genlarning ekspressionini tartibga solishning ushbu yangi mexanizmi, aslida, eukaryotik xromosomada minglab bunday triplekslar mavjudligini hisobga olgan holda, promotordan foydalanishni boshqarishning keng tarqalgan usulini aks ettirishi mumkin.[71] U1 ncRNA maxsus bog'lanish va stimulyatsiya qilish orqali transkripsiyani boshlashni keltirib chiqarishi mumkin TFIIH RNAP II ning C-terminal domenini fosforilatlash uchun.[72] NcRNA 7SK dan farqli o'laroq, transkripsiyaning cho'zilishini repressiya bilan birgalikda HEXIM1 /2, oldini olgan harakatsiz kompleks hosil qiladi PTEFb RNAP II ning C-terminal domenini fosforillaydigan umumiy transkripsiya omili,[72][73][74] shu bilan stressli sharoitda global uzayishni bostirish. O'zgarishlarni to'g'ridan-to'g'ri boshlash va cho'zish transkripsiyasi mexanizmi darajasida vositachilik qilish uchun individual promouterlarda tartibga solishning o'ziga xos rejimlarini chetlab o'tadigan ushbu misollar gen ekspressionidagi global o'zgarishlarga tez ta'sir ko'rsatadigan vositani taqdim etadi.

Global o'zgarishlarga tezda vositachilik qilish qobiliyati, kodlanmaydigan takrorlanadigan ketma-ketliklarni tezkor ifodalashda ham namoyon bo'ladi. Qisqa interfaol yadro (Sinus ) Alu elementlari odamlarda va sichqonlardagi o'xshash B1 va B2 elementlari genomlar ichida eng ko'p harakatlanadigan elementlarga aylanishga muvaffaq bo'lishdi, ular odamning ~ 10% va sichqon genomining ~ 6% ni o'z ichiga olgan.[75][76] Ushbu elementlar ncRNA sifatida transkripsiyalanadi RNAP III issiqlik zarbasi kabi ekologik stresslarga javoban,[77] bu erda ular yuqori yaqinlik bilan RNAP II bilan bog'lanib, faol boshlang'ichgacha bo'lgan komplekslarning shakllanishiga to'sqinlik qiladi.[78][79][80][81] Bu stressga javoban gen ekspressionining keng va tezkor repressiyasiga imkon beradi.[78][81]

Alu RNK transkriptlari ichidagi funktsional ketma-ketliklarni ajratish oqsil transkripsiyasi omillarida domenlarni tashkil etishga o'xshash modulli tuzilmani ishlab chiqdi.[82] Alu RNK tarkibida ikkita "qo'l" mavjud bo'lib, ularning har biri bittadan RNAP II molekulasini, shuningdek, in vitro ravishda RNAP II transkripsiyaviy repressiyasi uchun mas'ul bo'lgan ikkita tartibga soluvchi sohani birlashtirishi mumkin.[81] Ushbu ikkita erkin tuzilgan domenlar hatto repressiv rolini berish uchun B1 elementlari kabi boshqa ncRNA-lar bilan birlashtirilishi mumkin.[81] Alu elementlari va shunga o'xshash takrorlanadigan elementlarning sutemizuvchilar genomida ko'pligi va tarqalishi qisman ushbu funktsional domenlarning evolyutsiya jarayonida boshqa uzoq ncRNKlarga qo'shilib ketishi bilan bog'liq bo'lishi mumkin, bunda funktsional takroriy ketma-ketlik domenlari borligi ma'lum bo'lgan uzoq vaqt davomida odatiy xususiyatga ega. ncRNA, shu jumladan Kcnq1ot1, Xlsirt va Xist.[83][84][85][86]

Ga qo'shimcha sifatida issiqlik zarbasi, ning ifodasi Sinus elementlar (shu jumladan Alu, B1 va B2 RNKlari) virusli infektsiya kabi uyali stress paytida ko'payadi[87] ba'zi saraton hujayralarida[88] bu erda ular xuddi shunday gen ekspressionidagi global o'zgarishlarni tartibga solishi mumkin. Alu va B2 RNK ning to'g'ridan-to'g'ri RNAP II bilan bog'lanish qobiliyati transkripsiyani bosishning keng mexanizmini ta'minlaydi.[79][81] Shunga qaramay, Alu yoki B2 RNKlari induksiyaga uchragan genlarning faollashtirilgan promouterlarida, masalan, issiqlik shoki genlarida topilmaydigan ushbu global javob uchun alohida istisnolar mavjud.[81] Umumiy repressiyadan individual genlarni ozod qiladigan tartibga solishning ushbu qo'shimcha ierarxiyasi uzoq ncRNA, issiqlik shoki RNK-1 (HSR-1) ni ham o'z ichiga oladi. HSR-1 sutemizuvchilar hujayralarida faol bo'lmagan holatda bo'ladi, ammo stress ta'sirida issiqlik shoki genlarining ekspressionini keltirib chiqarish uchun faollashadi, degan fikr ilgari surildi.[89] Mualliflar ushbu faollashuv HSR-1 strukturasining konstruktiv o'zgarishini o'z ichiga oladi, bu esa haroratning ko'tarilishiga javoban, shu bilan keyinchalik trimerizatsiyaga uchragan va issiqlik zarbasi genlarining ekspressionini keltirib chiqaradigan transkripsiya faollashtiruvchisi HSF-1 bilan o'zaro aloqada bo'lishiga imkon beradi.[89] Keng ma'noda, ushbu misollar Alc yoki B2 RNKlari umumiy gen ekspressionini bosim o'tkazadigan ncRNAs ichiga joylashtirilgan tartibga solish sxemasini aks ettiradi, boshqa ncRNAlar esa o'ziga xos genlarning ekspressionini faollashtiradi.

RNK polimeraza III tomonidan yozilgan

Umumiy transkripsiya omillari yoki RNAP II bilan o'zaro ta'sir qiluvchi ncRNAlarning ko'pi (shu jumladan 7SK, Alu va B1 va B2 RNKlari) RNAP III tomonidan transkripsiyalanadi,[90] shu bilan ular boshqaradigan RNAP II transkripsiya reaktsiyasidan ushbu ncRNAlarning ekspresiyasini ajratib turadi. RNAP III shuningdek BC2 kabi bir qator qo'shimcha yangi ncRNAlarni transkripsiya qiladi, Miloddan avvalgi 200 yil tRNA, 5S rRNA va snRNAs kabi yuqori darajada ifoda etilgan infratuzilmaviy "uyni saqlash" ncRNA genlaridan tashqari, ba'zi mikroRNKlar va snoRNAlar.[90] RNAP II ga bog'liq bo'lgan sherigini boshqaradigan RNAP III ga bog'liq ncRNA transkriptomining mavjudligi yaqinda o'tkazilgan bir tadqiqot tomonidan qo'llab-quvvatlandi, RNAP III tomonidan transkripsiyalangan ncRNAlarning yangi to'plamini oqsillarni kodlovchi genlarga ketma-ket homologiyasi bilan tasvirlab berdi. Bu mualliflarni "kogen / gen" funktsional tartibga solish tarmog'ini yaratishga undadi,[91] ushbu ncRNAlardan biri, 21A antisensens sherik genining ekspressionini boshqarishini ko'rsatib, CENP-F transda

Transkripsiyadan keyingi tartibga solishda

Transkripsiyani tartibga solishdan tashqari, ncRNAlar transkripsiyadan keyingi mRNKni qayta ishlashning turli jihatlarini ham nazorat qiladi. MikroRNK va snoRNA kabi kichik tartibga soluvchi RNKlarga o'xshab, bu funktsiyalar ko'pincha maqsad mRNK bilan bir-birini to'ldiruvchi bazaviy juftlikni o'z ichiga oladi. Bir-birini to'ldiruvchi ncRNA va mRNA o'rtasida RNK duplekslarining hosil bo'lishi trans-ta'sir qiluvchi omillarni bog'lash uchun zarur bo'lgan mRNK tarkibidagi asosiy elementlarni maskalashi mumkin, bu esa mRNKni qayta ishlash va qo'shish, tashish, tarjima va degradatsiyani o'z ichiga olgan transkripsiyadan keyingi gen ekspresiyasining har qanday bosqichiga ta'sir qilishi mumkin.[92]

Birlashtirishda

The biriktirish mRNK uning tarjimasini keltirib chiqarishi va o'zi kodlaydigan oqsillarning repertuarini funktsional ravishda diversifikatsiya qilishi mumkin. The Zeb2 mRNA, ayniqsa uzoq 5'UTR ga ega, samarali tarjima qilish uchun ichki ribosoma kirish joyini o'z ichiga olgan 5'UTR intronini saqlashni talab qiladi.[93] Shu bilan birga, intronni ushlab turish intronik 5 'qo'shilish joyini to'ldiradigan antisens transkriptning ifodasiga bog'liq.[93] Shuning uchun antisens transkriptning ektopik ifodasi qo'shilishni bostiradi va mezenximal rivojlanish jarayonida Zeb2 mRNA ning tarjimasini keltirib chiqaradi. Xuddi shu tarzda, anti-antisense Rev-ErbAa2 transkriptining ifodasi ikkita antagonistik izoformni hosil qilish uchun qalqonsimon gormon retseptorlari ErbAa2 mRNA ning muqobil biriktirilishini boshqaradi.[94]

Tarjimada

NcRNA, shuningdek, qo'shimcha tartibga solish bosimini qo'llashi mumkin tarjima, xususan neyronlarda ekspluatatsiya qilinadigan xususiyat, bu erda mRNKning dendritik yoki aksonal tarjimasi sinaptik faollikka javoban sinaptik plastisitning o'zgarishiga va neyron tarmoqlarini qayta tuzilishiga yordam beradi. Ilgari tRNKlardan olingan RNAP III transkripsiyasi bo'lgan BC1 va BC200 ncRNA'lari mos ravishda sichqonchada va insonning markaziy asab tizimida ifodalanadi.[95][96] BC1 ekspressioni sinaptik faollik va sinaptogenezga javoban indüklenir va ayniqsa, neyronlardagi dendritlarga qaratilgan.[97] BC1 va turli xil neyronlarga xos mRNK mintaqalari o'rtasidagi ketma-ketlikni to'ldirish, shuningdek, maqsadli tarjima repressiyasida BC1 uchun rol o'ynaydi.[98] Darhaqiqat, yaqinda BC1 dopamin samaradorligini boshqarish uchun dendritlarda translyatsion repressiya bilan bog'liqligi ko'rsatildi D2 retseptorlari vositasida uzatilishi striatum[99] va BC1 RNK bilan o'chirilgan sichqonlar kashfiyotni kamaytirishi va xavotirning kuchayishi bilan xatti-harakatlarda o'zgarishlarni namoyish etadi.[100]

SiRNA yo'naltirilgan genlarni boshqarishda

Bir qatorli RNK tarkibidagi asosiy elementlarni maskalashdan tashqari, ikki zanjirli RNK duplekslarining hosil bo'lishi Drosophila va sichqoncha oositlarida endogen siRNA (endo-siRNA) hosil bo'lishi uchun substrat ham berishi mumkin.[101] Bir-birini to'ldiruvchi ketma-ketliklar, masalan, transkriptlar orasidagi antisensiya yoki takrorlanadigan mintaqalar kabi tavlanish, Dicer-2 tomonidan endo-siRNKlarga ishlov berilishi mumkin bo'lgan RNK dupleksini hosil qiladi. Shuningdek, kengaytirilgan molekula ichidagi soch turmaklarini hosil qiluvchi uzun ncRNKlar siRNKlarga qayta ishlanib, esi-1 va esi-2 transkriptlari bilan juda yaxshi tasvirlangan bo'lishi mumkin.[102] Ushbu transkriptlardan hosil bo'lgan Endo-siRNAlar, ayniqsa, ko'chib o'tuvchi transpozon elementlarning genom ichida tarqalishini bostirishda foydalidir. Shu bilan birga, antisense transkriptlaridan endo-siRNA hosil bo'lishi yoki pseudogenlar shuningdek, ularning funktsional o'xshashlarining RISC effektorli komplekslari orqali ifodasini o'chirishi mumkin, bu misol sifatida uzoq va qisqa RNK regulyatsiyasining turli xil rejimlarini birlashtirgan muhim tugun vazifasini bajaradi. Xist va Tsix (yuqoriga qarang).[103]

Epigenetik regulyatsiyada

Epigenetik modifikatsiyalar, shu jumladan giston va DNK metilatsiyasi, giston atsetilatsiyasi va sumoyillanishi xromosoma biologiyasining ko'p jihatlariga ta'sir qiladi, birinchi navbatda keng xromatin domenlarini qayta qurish orqali ko'p sonli genlarni boshqarishni o'z ichiga oladi.[104][105] RNK xromatinning ajralmas qismi ekanligi ma'lum bo'lgan bo'lsa-da,[106][107] yaqinda biz RNK xromatin modifikatsiyasi yo'llarida ishtirok etadigan vositalarni qadrlay boshladik.[108][109][110] Masalan, Oplr16 epigenetik ravishda aktivatsiyasini keltirib chiqaradi ildiz hujayrasi intrakromozomani muvofiqlashtirish orqali asosiy omillar pastadir va ishga qabul qilish DNK demetilaza TET2.[111]

Drosophila-da uzun ncRNAlar tromotoraks oqsilining xromatin modifikatsiyalash funktsiyalarini jalb qilish va yo'naltirish orqali gomeotik gen Ubx ekspressionini keltirib chiqaradi. Xox tartibga soluvchi elementlar.[110] Xuddi shunday modellar ham insoniyat taraqqiyoti davomida saqlanib turadigan Xox genlarining embrional ekspression profillari asosida kuchli epigenetik mexanizmlar yotadi deb o'ylaydigan sutemizuvchilardan taklif qilingan.[112][109] Darhaqiqat, odamning Hox genlari insoniyat rivojlanishining fazoviy va vaqtinchalik o'qlari bo'ylab ketma-ket ifodalangan yuzlab ncRNKlar bilan bog'langan va differentsial giston metilatsiyasining xromatin domenlarini va RNK polimeraza mavjudligini aniqlaydi.[109] HOXC lokusidan kelib chiqqan HOTAIR deb nomlangan bitta ncRNA, xromatin trimetilatsiya holatini o'zgartirib, 40 kb HOXD lokusidagi transkripsiyani bosadi. HOTAIR, bunga hujayralarning epigenetik holatini va keyingi genlarning ekspresiyasini boshqarish uchun transkompaniyada Polycomb xromatinni qayta qurish komplekslari ta'sirini yo'naltirish orqali erishadi deb o'ylashadi. Suz12, EZH2 va EEDni o'z ichiga olgan Polycomb kompleksining tarkibiy qismlari, HOTAIR va, ehtimol, boshqa shunga o'xshash ncRNA-larni bog'lashi mumkin bo'lgan RNK bilan bog'lanish domenlarini o'z ichiga oladi.[113][114] Ushbu misol ncRNAlar yaqinda chop etilgan genomik xaritalarning murakkabligini ta'kidlab, o'ziga xos genomik joylarga o'zgartiradigan xromatinli oqsillarni o'zgartiradigan umumiy to'plam funktsiyasini jalb qiladigan kengroq mavzuni yaxshi tasvirlaydi.[105] Darhaqiqat, oqsillarni kodlovchi genlar bilan bog'liq bo'lgan uzoq ncRNAlarning tarqalishi rivojlanish jarayonida genlarning ekspressionini tartibga soluvchi xromatin modifikatsiyasining lokalizatsiya namunalariga hissa qo'shishi mumkin. Masalan, oqsillarni kodlovchi genlarning aksariyatida antisensli sheriklar mavjud, shu qatorda saraton kasalligida epigenetik mexanizmlar bilan tez-tez jim bo'lib turadigan ko'plab o'smani bostiruvchi genlar.[115] Yaqinda o'tkazilgan bir tadqiqot leykemiyada p15 genining teskari ekspression profilini va antisense ncRNA ni kuzatdi.[115] Batafsil tahlil p15 antisense ncRNA (CDKN2BAS ) noma'lum mexanizm yordamida geteroxromatin va p15 DNK metilatlanish holatiga o'zgarishlarni kiritishga muvaffaq bo'ldi va shu bilan p15 ekspressionini tartibga keltirdi.[115] Shu sababli, bog'langan antisense ncRNA-larning misekspressioni keyinchalik saraton kasalligiga sabab bo'lgan o'simta supressor genini susaytirishi mumkin.

Imprinting

NcRNA-ga asoslangan xromatin modifikatsiyasining ko'plab paydo bo'lgan mavzulari birinchi bo'lib fenomen ichida namoyon bo'ldi bosib chiqarish, bu bilan genning faqat bitta alleli onalik yoki otalik xromosomasidan ifodalanadi. Umuman olganda, imprintlangan genlar xromosomalarda birlashtirilgan bo'lib, imprinting mexanizmi individual genlarga emas, balki mahalliy xromosoma domenlariga ta'sir qiladi. Ushbu klasterlar ko'pincha bir xil alleldagi bog'langan oqsillarni kodlovchi genning repressiyasi bilan bog'liq bo'lgan uzun ncRNKlar bilan bog'liq.[116] Darhaqiqat, batafsil tahlil ncRNA Kcnqot1 va Igf2r / Air uchun imprintingni boshqarishda hal qiluvchi rolni ochib berdi.[117]

Kcnq1 lokusidagi deyarli barcha genlar ona tomonidan meros bo'lib olinadi, faqat otadan ifodalangan antisens ncRNA Kcnqot1 bundan mustasno.[118] Kesilgan Kcnq1ot bilan transgenik sichqonlar qo'shni genlarni susaytira olmaydilar, shuning uchun Kcnqot1 genlarning otalik xromosomasida iz qoldirishi uchun juda muhimdir.[119] Ko'rinib turibdiki, Kcnqot1 lizin 9 (H3K9me3) va 27 giston 3 ning trimetilatsiyasini boshqarishga qodir (H3K27me3 ) Kcnqot1 promouteri bilan ustma-ust keladigan va aslida Kcnq1 sense exon ichida joylashgan imprinting markaziga.[120] HOTAIR-ga o'xshash (yuqoriga qarang), Eed-Ezh2 Polycomb komplekslari Kcnq1 lokus otasining xromosomasiga, ehtimol Kcnqot1 tomonidan qabul qilinadi, bu erda ular repressiv giston metilatsiyasi orqali genlarni susaytirishda vositachilik qilishlari mumkin.[120] Differentsial metillangan imprinting markazi, shuningdek, otaning xromosomasidagi Igf2r joyida qo'shni genlarning sukutlanishiga javobgar bo'lgan uzoq antisense ncRNA Air promouteri bilan ustma-ust tushadi.[121][122] Igf2r joyida allelga xos histon metilatsiyasining mavjudligi shuni ko'rsatadiki, havo xromatin modifikatsiyasi orqali sustlashda vositachilik qiladi.[123]

Xist va X-xromosomalarning inaktivatsiyasi

Platsenta ayol sutemizuvchilarida X-xromosomaning inaktivatsiyasini eng qadimgi va eng yaxshi xarakterlangan uzun ncRNAlardan biri boshqaradi, Xist.[124] Xistning kelajakdagi harakatsiz X-xromosomadan ifodalanishi va keyinchalik faol bo'lmagan X-xromosomaning qoplanishi embrionning ildiz hujayralari differentsiatsiyasi paytida yuzaga keladi. Xist ekspressionidan keyin xromatin modifikatsiyasining qaytarilmas qatlamlari kuzatiladi, ular tarkibiga histon (H3K9) atsetilatsiyasining yo'qolishi va faol xromatin bilan bog'liq bo'lgan H3K4 metilatsiyasi kiradi va repressiv xromatin modifikatsiyasini induksiyasi shu jumladan H4 gipoatsetillanish, H3K27 trimetilatsiya,[124] H3K9 gipermetillanish va H4K20 monometillanish, shuningdek H2AK119 monoubiquitylation. Ushbu modifikatsiyalar X bilan bog'langan genlarning transkripsiyaviy sukunatiga to'g'ri keladi.[125] Xist RNK, shuningdek, faol bo'lmagan X-xromosomaga giston varianti makroH2A ni joylashtiradi.[126] Xist lokuslarida mavjud bo'lgan qo'shimcha ncRNAlar mavjud, shu jumladan antisik transkripsiyasi Tsix, bu kelajakdagi faol xromosomadan ifoda etilgan va Xist ekspressionini endogen siRNA hosil bo'lishi bilan bostirishga qodir.[103] Ushbu ncRNA-lar birgalikda ayol sutemizuvchilarda faqat bitta X-xromosoma faol bo'lishini ta'minlaydi.

Telomerik kodlamaydigan RNKlar

Telomerlar sutemizuvchilar xromosomalarining terminal mintaqasini tashkil qiladi va barqarorlik va qarish uchun juda muhimdir va saraton kabi kasalliklarda markaziy rol o'ynaydi.[127] Telomerlar uzoq vaqtdan beri transkripsiyaviy ravishda inert DNK-oqsil komplekslari deb hisoblanib, 2000-yillarning oxirlarida telomerik takrorlanishlar telomerik RNK (TelRNA) sifatida yozilishi mumkinligi ko'rsatilgunga qadar.[128] yoki takroriy tarkibidagi telomerik RNKlar.[129] Ushbu ncRNKlar uzunligi bo'yicha heterojen bo'lib, bir nechta sub-telomerik lokuslardan transkripsiyalanadi va jismonan telomerlarga joylashadi. Ularning telomerga xos heteroxromatin modifikatsiyasini boshqarishda ishtirok etishini ko'rsatadigan xromatin bilan aloqasi SMM oqsillari tomonidan siqib chiqarilib, xromosomalarning uchlarini telomerlarning yo'qolishidan himoya qiladi.[129] Bundan tashqari, TelRNAlar telomeraza faolligini in vitro bloklaydi va shuning uchun telomeraza faolligini tartibga solishi mumkin.[128] Erta bo'lsa ham, ushbu tadqiqotlar telomer biologiyasining turli jihatlarida telomerik ncRNA-larga aloqadorligini ko'rsatadi.

DNK replikatsiyasi vaqtini va xromosoma barqarorligini boshqarishda

Asenkron ravishda takrorlanadigan autosomal RNKlar (ASAR) juda uzun (~ 200kb) kodlanmaydigan RNKlar, ular biriktirilmagan, poliadenilatsiz va DNK replikatsiyasining normal muddati va xromosomalarning barqarorligi uchun zarurdir.[130][131][132] ASAR6, ASAR15 yoki ASAR6-141 ni o'z ichiga olgan genetik lokuslardan birini o'chirib tashlash natijasida butun xromosomaning kechiktirilgan replikatsiya vaqti va kechiktirilgan mitoz kondensatsiyasi (DRT / DMC) bir xil fenotipga olib keladi. DRT / DMC, ikkinchi darajali qayta tashkil etish chastotasi va beqaror xromosomaga olib keladigan xromosoma ajratish xatolariga olib keladi. Xistga o'xshab, ASAR tasodifiy monoallel ekspressionni namoyish etadi va DNKning asenkron replikatsiya sohalarida mavjud. ASAR funktsiyasi mexanizmi hanuzgacha o'rganilayotgan bo'lsa-da, ular Xist lncRNA kabi mexanizmlar orqali ishlaydi, ammo genlarning ekspresiyasida allelga xos o'zgarishlarni keltirib chiqaradigan kichik avtosomal domenlarda ishlaydi.

Qarish va kasalliklarda

So'nggi paytlarda uzoq ncRNKlarning hujayra biologiyasining turli jabhalarida ishlashini tan olish ularning e'tiborini kasallik etiologiyasiga hissa qo'shish imkoniyatlariga qaratdi. 80% dan ortig'i (1867 lncRNA orasida 1502 LncBook ) eksperimental ravishda o'rganilgan lnkRNKlarning 462 kasallik va 28 MeSH kasallik atamasi bilan bog'liqligi va 97,998 lncRNKning ko'p omikli dalillarga asoslangan kasalliklarga aloqadorligi haqida xabar berilgan.[15] Bir nechta tadqiqotlar uzoq ncRNKlarni turli xil kasalliklarga duchor qildi va nevrologik kasalliklar va saraton kasalliklarida ishtirok etish va hamkorlikni qo'llab-quvvatladi.

Qarish va inson nevrologik kasalliklarida lncRNA ko'pligining o'zgarishi to'g'risida birinchi nashr qilingan hisobot Lukiw va boshq.[133] o'limdan keyingi qisqa muddatli Altsgeymer kasalligi va Altsgeymer bo'lmagan demans (NAD) to'qimalaridan foydalangan holda o'tkazilgan tadqiqotda; ushbu dastlabki ish 1987 yilda BC200 (miya, sitoplazmik, 200 nukleotid) deb nomlanuvchi Uotson va Satklif tomonidan Alu takroriy oilasining primat miyaga xos sitoplazmik transkriptini oldindan aniqlashga asoslangan edi.[134]

Uzoq kodlamaydigan RNKlar immun hujayralari biologiyasidagi NOTCH, PAX5, MYC va EZH2 kabi asosiy omillarga ta'sir qiladi va shu bilan adaptiv va tug'ma immunitetni tartibga soladi.[135] LncRNAs NFAT, NFκB, MYC, interferon va TCR / BCR signalizatsiyasi kabi yo'llarni va hujayra effektori funktsiyalarini (IFNG-AS1, TH2-LCR) tartibga solish orqali limfotsitlar faollashishini (NRON, NKILA, BCALM, GAS5, PVT1) modulyatsiya qiladi. Bu shuningdek, otoimmun kasalliklar (multipl skleroz, yallig'lanishli ichak kasalligi, revmatoid artrit) va T / B hujayra leykemiyalari va limfomalari (CLL, MCL, DLBCL, T-ALL) biologiyasiga ta'sir qiladi.[135]

Ko'pgina assotsiatsiya tadqiqotlari kasallik holatlarida uzoq ncRNAlarning g'ayrioddiy ekspresiyasini aniqlagan bo'lsa-da, ularning kasallik keltirib chiqaradigan roli haqida juda kam tushuncha mavjud. O'simta hujayralari va normal hujayralarni taqqoslaydigan ekspression tahlillari saratonning bir nechta shakllarida ncRNK ekspresiyasining o'zgarishini aniqladi. Masalan, prostata bezining o'smalarida, PCGEM1 (haddan tashqari ta'sirlangan ikki ncRNA ning biri) ko'payish va koloniya shakllanishi bilan bog'liq bo'lib, hujayra o'sishini boshqarishda ishtirok etishni anglatadi.[136] MALAT1 (shuningdek, NEAT2 nomi bilan ham tanilgan) dastlab o'pkaning kichik bosqichli hujayrali bo'lmagan saraton kasalligining metastazida yuqori darajada ifoda etilgan ncRNA deb aniqlangan va uning haddan tashqari ekspressioni bemorning omon qolish darajasi past prognostik belgidir.[136] Yaqinda MALAT1 ning yuqori konservalangan sichqonchani gomologi gepatotsellulyar karsinomada yuqori darajada namoyon bo'lganligi aniqlandi.[137] Prostata bezi saratoni namunalarida o'smaning differentsiatsiyasi darajasiga bog'liq ekspresyonga ega bo'lgan intronik antisense ncRNKlari ham qayd etilgan.[138] Bir qator uzoq ncRNKlarning saraton kasalligida ekspression ifodasiga ega bo'lishiga qaramay, ularning faoliyati va tumourogenezdagi potentsial roli nisbatan noma'lum. Masalan, HIS-1 va BIC ncRNAs saraton rivojlanishida va o'sishini nazorat qilishda ishtirok etgan, ammo ularning normal hujayralardagi faoliyati noma'lum.[139][140] Saraton kasalligidan tashqari, ncRNKlar boshqa kasallik holatlarida ham nomuvofiq ekspressionni namoyon etadi. PRINSning haddan tashqari namoyon bo'lishi psoriazga moyilligi bilan bog'liq bo'lib, psoriatik bemorlarning jalb qilinmagan epidermisida PRINS ekspressioni ikkala psoriatik lezyon va sog'lom epidermis bilan solishtirganda ko'tariladi.[141]

Genom miqyosidagi profilaktika shuni ko'rsatdiki, ko'plab transkripsiyalangan ultrakonservlangan mintaqalar odamlarning saraton kasalligi holatlarida turli xil profillarni namoyish etadi.[64] An analysis of chronic lymphocytic leukaemia, colorectal carcinoma and hepatocellular carcinoma found that all three cancers exhibited aberrant expression profiles for ultraconserved ncRNAs relative to normal cells. Further analysis of one ultraconserved ncRNA suggested it behaved like an oncogene by mitigating apoptosis and subsequently expanding the number of malignant cells in colorectal cancers.[64] Many of these transcribed ultraconserved sites that exhibit distinct signatures in cancer are found at fragile sites and genomic regions associated with cancer. It seems likely that the aberrant expression of these ultraconserved ncRNAs within malignant processes results from important functions they fulfil in normal human development.

Recently, a number of association studies examining single nucleotide polymorphisms (SNPs) associated with disease states have been mapped to long ncRNAs. For example, SNPs that identified a susceptibility locus for myocardial infarction mapped to a long ncRNA, MIAT (myocardial infarction associated transcript).[142] Likewise, genome-wide association studies identified a region associated with coronary artery disease[143] that encompassed a long ncRNA, ANRIL.[144] ANRIL is expressed in tissues and cell types affected by atherosclerosis[145][146] and its altered expression is associated with a high-risk haplotype for coronary artery disease.[146][147]

The complexity of the transcriptome, and our evolving understanding of its structure may inform a reinterpretation of the functional basis for many natural polymorphisms associated with disease states. Many SNPs associated with certain disease conditions are found within non-coding regions and the complex networks of non-coding transcription within these regions make it particularly difficult to elucidate the functional effects of polymorphisms. For example, a SNP both within the truncated form of ZFAT and the promoter of an antisense transcript increases the expression of ZFAT not through increasing the mRNA stability, but rather by repressing the expression of the antisense transcript.[148]

The ability of long ncRNAs to regulate associated protein-coding genes may contribute to disease if misexpression of a long ncRNA deregulates a protein coding gene with clinical significance. In similar manner, an antisense long ncRNA that regulates the expression of the sense BACE1 gene, a crucial enzyme in Alzheimer’s disease etiology, exhibits elevated expression in several regions of the brain in individuals with Alzheimer's disease[149] Alteration of the expression of ncRNAs may also mediate changes at an epigenetic level to affect gene expression and contribute to disease aetiology. For example, the induction of an antisense transcript by a genetic mutation led to DNA methylation and silencing of sense genes, causing ß-thalassemia in a patient.[150]

Shuningdek qarang

Adabiyotlar

  1. ^ Perkel JM (June 2013). "Visiting "noncodarnia"". Biotexnikalar (qog'oz). 54 (6): 301, 303–4. doi:10.2144/000114037. PMID  23750541. "We're calling long noncoding RNAs a class, when actually the only definition is that they are longer than 200 bp," says Ana Marques, a Research Fellow at the University of Oxford who uses evolutionary approaches to understand lncRNA function.
  2. ^ Ma L, Bajic VB, Zhang Z (June 2013). "On the classification of long non-coding RNAs". RNK biologiyasi. 10 (6): 925–933. doi:10.4161/rna.24604. PMC  4111732. PMID  23696037.
  3. ^ Julia D. Ransohoff, Yuning Wei & Paul A. Khavari (2018). "The functions and unique features of long intergenic non-coding RNA". Molekulyar hujayra biologiyasi. 19 (3): 143–157 (2018). doi:10.1038/nrm.2017.104. PMC  5889127. PMID  29138516.
  4. ^ a b Kapranov P, Cheng J, Dike S, Nix DA, Duttagupta R, Willingham AT, Stadler PF, Hertel J, Hackermüller J, Hofacker IL, Bell I, Cheung E, Drenkow J, Dumais E, Patel S, Helt G, Ganesh M, Ghosh S, Piccolboni A, Sementchenko V, Tammana H, Gingeras TR (June 2007). "RNA maps reveal new RNA classes and a possible function for pervasive transcription". Ilm-fan. 316 (5830): 1484–1488. Bibcode:2007Sci...316.1484K. doi:10.1126/science.1138341. PMID  17510325.
  5. ^ a b v d Carninci P, Kasukawa T, Katayama S, Gough J, Frith MC, Maeda N, et al. (2005 yil sentyabr). "Sutemizuvchilar genomining transkripsiyaviy manzarasi". Ilm-fan. 309 (5740): 1559–1563. Bibcode:2005 yil ... 309.1559F. doi:10.1126 / science.1112014. PMID  16141072.
  6. ^ Cheng J, Kapranov P, Drenkow J, Dike S, Brubaker S, Patel S, Long J, Stern D, Tammana H, Helt G, Sementchenko V, Piccolboni A, Bekiranov S, Bailey DK, Ganesh M, Ghosh S, Bell I, Gerhard DS, Gingeras TR (May 2005). "5 ta nukleotid rezolyusiyasida odamning 10 ta xromosomasining transkripsiyaviy xaritalari". Ilm-fan. 308 (5725): 1149–1154. Bibcode:2005 yil ... 308.1149C. doi:10.1126 / science.1108625. PMID  15790807.
  7. ^ a b Necsulea A, Soumillon M, Warnefors M, Liechti A, Daish T, Zeller U, Baker JC, Grützner F, Kaessmann H (January 2014). "The evolution of lncRNA repertoires and expression patterns in tetrapods". Tabiat. 505 (7485): 635–640. Bibcode:2014Natur.505..635N. doi:10.1038/nature12943. PMID  24463510.
  8. ^ a b v Derrien T, Johnson R, Bussotti G, Tanzer A, Djebali S, Tilgner H, Guernec G, Martin D, Merkel A, Knowles DG, Lagarde J, Veeravalli L, Ruan X, Ruan Y, Lassmann T, Carninci P, Brown JB, Lipovich L, Gonzalez JM, Thomas M, Davis CA, Shiekhattar R, Gingeras TR, Hubbard TJ, Notredame C, Harrow J, Guigó R (September 2012). "GENCODE v7 katalogi insonning uzoq vaqt davomida kodlamaydigan RNKlari: ularning gen tuzilishi, evolyutsiyasi va ifodasini tahlil qilish". Genom tadqiqotlari. 22 (9): 1775–1789. doi:10.1101 / gr.132159.111. PMC  3431493. PMID  22955988.
  9. ^ Hon CC, Ramilowski JA, Harshbarger J, Bertin N, Rackham OJ, Gough J, Denisenko E, Schmeier S, Poulsen TM, Severin J, Lizio M, Kawaji H, Kasukawa T, Itoh M, Burroughs AM, Noma S, Djebali S, Alam T, Medvedeva YA, Testa AC, Lipovich L, Yip CW, Abugessaisa I, Mendez M, Hasegawa A, Tang D, Lassmann T, Heutink P, Babina M, Wells CA, Kojima S, Nakamura Y, Suzuki H, Daub CO, de Hoon MJ, Arner E, Hayashizaki Y, Carninci P, Forrest AR (March 2017). "An atlas of human long non-coding RNAs with accurate 5′ ends". Tabiat. 543 (7644): 199–204. Bibcode:2017Natur.543..199H. doi:10.1038/nature21374. PMC  6857182. PMID  28241135.
  10. ^ a b Cabili MN, Trapnell C, Goff L, Koziol M, Tazon-Vega B, Regev A, Rinn JL (September 2011). "Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses". Genlar va rivojlanish. 25 (18): 1915–1927. doi:10.1101/gad.17446611. PMC  3185964. PMID  21890647.
  11. ^ Ravasi T, Suzuki H, Pang KC, Katayama S, Furuno M, Okunishi R, Fukuda S, Ru K, Frith MC, Gongora MM, Grimmond SM, Hume DA, Hayashizaki Y, Mattick JS (January 2006). "Experimental validation of the regulated expression of large numbers of non-coding RNAs from the mouse genome". Genom tadqiqotlari. 16 (1): 11–19. doi:10.1101/gr.4200206. PMC  1356124. PMID  16344565.
  12. ^ Yunusov D, Anderson L, DaSilva LF, Wysocka J, Ezashi T, Roberts RM, Verjovski-Almeida S (September 2016). "HIPSTR and thousands of lncRNAs are heterogeneously expressed in human embryos, primordial germ cells and stable cell lines". Ilmiy ma'ruzalar. 6: 32753. Bibcode:2016NatSR...632753Y. doi:10.1038/srep32753. PMC  5015059. PMID  27605307.
  13. ^ Yan L, Yang M, Guo H, Yang L, Wu J, Li R, Liu P, Lian Y, Zheng X, Yan J, Huang J, Li M, Wu X, Wen L, Lao K, Li R, Qiao J, Tang F (September 2013). "Single-cell RNA-Seq profiling of human preimplantation embryos and embryonic stem cells". Tabiatning strukturaviy va molekulyar biologiyasi. 20 (9): 1131–1139. doi:10.1038/nsmb.2660. PMID  23934149.
  14. ^ Liu SJ, Nowakowski TJ, Pollen AA, Lui JH, Horlbeck MA, Attenello FJ, He D, Weissman JS, Kriegstein AR, Diaz AA, Lim DA (April 2016). "Single-cell analysis of long non-coding RNAs in the developing human neocortex". Genom biologiyasi. 17: 67. doi:10.1186/s13059-016-0932-1. PMC  4831157. PMID  27081004.
  15. ^ a b v d Ma L, Cao J, Liu L, Du Q, Li Z, Zou D, Bajic VB, and Zhang Z (Jan 2019). "LncBook: a curated knowledgebase of human long non-coding RNAs". Nuklein kislotalarni tadqiq qilish. 47 (Database issue): D128–D134. doi:10.1093/nar/gky960. PMC  6323930. PMID  30329098.
  16. ^ Paytuví Gallart A, Hermoso Pulido A, Anzar Martínez de Lagrán I, Sanseverino W, Aiese Cigliano R (January 2016). "GREENC: a Wiki-based database of plant lncRNAs". Nuklein kislotalarni tadqiq qilish. 44 (D1): D1161–6. doi:10.1093/nar/gkv1215. PMC  4702861. PMID  26578586.
  17. ^ Kapranov P, Willingham AT, Gingeras TR (June 2007). "Genome-wide transcription and the implications for genomic organization". Genetika haqidagi sharhlar. 8 (6): 413–423. doi:10.1038/nrg2083. PMID  17486121.
  18. ^ Birney E, Stamatoyannopoulos JA, Dutta A, Guigó R, Gingeras TR, Margulies EH, et al. (2007 yil iyun). "ENCODE pilot loyihasi bo'yicha inson genomidagi 1% funktsional elementlarni aniqlash va tahlil qilish". Tabiat. 447 (7146): 799–816. Bibcode:2007 yil natur.447..799B. doi:10.1038 / nature05874. PMC  2212820. PMID  17571346.
  19. ^ Camargo, Antonio P; Sourkov, Vsevolod; Pereira, Gonçalo A G; Carazzolle, Marcelo F (2020-03-01). "RNAsamba: neural network-based assessment of the protein-coding potential of RNA sequences". NAR Genomikasi va Bioinformatikasi. 2 (1): lqz024. doi:10.1093/nargab/lqz024. ISSN  2631-9268.
  20. ^ Wang G, Yin H, Li B, Yu C, Wang F, Xu X, Cao J, Bao Y, Wang L, Abbasi AA, Bajic VB, Ma L, Zhang Z (January 2019). "Characterization and identification of long non-coding RNAs based on feature relationship". Bioinformatika. 41 (Database issue): D246–D251. doi:10.1093/bioinformatics/btz008. PMID  30649200.
  21. ^ Wang L, Park HJ, Dasari S, Wang S, Kocher JP, Li W (April 2013). "CPAT: Coding-Potential Assessment Tool using an alignment-free logistic regression model". Nuklein kislotalarni tadqiq qilish. 41 (6): e74. doi:10.1093/nar/gkt006. PMC  3616698. PMID  23335781.
  22. ^ Hu L, Xu Z, Hu B, Lu ZJ (January 2017). "COME: a robust coding potential calculation tool for lncRNA identification and characterization based on multiple features". Nuklein kislotalarni tadqiq qilish. 45 (1): e2. doi:10.1093/nar/gkw798. PMC  5224497. PMID  27608726.
  23. ^ Sun L, Liu H, Zhang L, Meng J (2015). "lncRScan-SVM: A Tool for Predicting Long Non-Coding RNAs Using Support Vector Machine". PLOS ONE. 10 (10): e0139654. Bibcode:2015PLoSO..1039654S. doi:10.1371/journal.pone.0139654. PMC  4593643. PMID  26437338.
  24. ^ a b Sun L, Luo H, Bu D, Zhao G, Yu K, Zhang C, Liu Y, Chen R, Zhao Y (September 2013). "Utilizing sequence intrinsic composition to classify protein-coding and long non-coding transcripts". Nuklein kislotalarni tadqiq qilish. 41 (17): e166. doi:10.1093/nar/gkt646. PMC  3783192. PMID  23892401.
  25. ^ Wucher, Valentin; Legeai, Fabrice; Hédan, Benoît; Rizk, Guillaume; Lagoutte, Lætitia; Leeb, Tosso; Jagannatan, Vidya; Cadieu, Edouard; David, Audrey (5 May 2017). "FEELnc: a tool for long non-coding RNA annotation and its application to the dog transcriptome". Nuklein kislotalarni tadqiq qilish. 45 (8): e57. doi:10.1093/nar/gkw1306. ISSN  1362-4962. PMC  5416892. PMID  28053114.
  26. ^ Lin MF, Jungreis I, Kellis M (July 2011). "PhyloCSF: a comparative genomics method to distinguish protein coding and non-coding regions". Bioinformatika. 27 (13): i275–i282. doi:10.1093/bioinformatics/btr209. PMC  3117341. PMID  21685081.
  27. ^ Deshpande S, Shuttleworth J, Yang J, Taramonli S, England M (February 2019). "PLIT: An alignment-free computational tool for identification of long non-coding RNAs in plant transcriptomic datasets". Biologiya va tibbiyotdagi kompyuterlar. 105: 169–181. arXiv:1902.05064. Bibcode:2019arXiv190205064D. doi:10.1016/j.compbiomed.2018.12.014. PMID  30665012.
  28. ^ Negri TD, Alves WA, Bugatti PH, Saito PT, Domingues DS, Paschoal AR (2019). "Pattern recognition analysis on long noncoding RNAs: a tool for prediction in plants". Bioinformatika bo'yicha brifinglar. 20 (2): 682–689. doi:10.1093/bib/bby034. PMID  29697740.
  29. ^ Singh U, Khemka N, Rajkumar MS, Garg R, Jain M (December 2017). "PLncPRO for prediction of long non-coding RNAs (lncRNAs) in plants and its application for discovery of abiotic stress-responsive lncRNAs in rice and chickpea". Nuklein kislotalarni tadqiq qilish. 45 (22): e183. doi:10.1093/nar/gkx866. PMC  5727461. PMID  29036354.
  30. ^ Simopoulos CM, Weretilnyk EA, Golding GB (May 2018). "Prediction of plant lncRNA by ensemble machine learning classifiers". BMC Genomics. 19 (1): 316. doi:10.1186/s12864-018-4665-2. PMC  5930664. PMID  29720103.
  31. ^ Chen J, Shishkin AA, Zhu X, Kadri S, Maza I, Guttman M, Hanna JH, Regev A, Garber M (Feb 2016). "Evolutionary analysis across mammals reveals distinct classes of long non-coding RNAs". Genom biologiyasi. 17 (19). doi:10.1186/s13059-016-0880-9. PMC  4739325. PMID  26838501.
  32. ^ Anderson DM, Anderson KM, Chang CL, Makarewich CA, Nelson BR, McAnally JR, Kasaragod P, Shelton JM, Liou J, Bassel-Duby R, Olson EN (February 2015). "A micropeptide encoded by a putative long noncoding RNA regulates muscle performance". Hujayra. 160 (4): 595–606. doi:10.1016/j.cell.2015.01.009. PMC  4356254. PMID  25640239.
  33. ^ Matsumoto A, Pasut A, Matsumoto M, Yamashita R, Fung J, Monteleone E, Saghatelian A, Nakayama KI, Clohessy JG, Pandolfi PP (January 2017). "mTORC1 and muscle regeneration are regulated by the LINC00961-encoded SPAR polypeptide". Tabiat. 541 (7636): 228–232. Bibcode:2017Natur.541..228M. doi:10.1038/nature21034. PMID  28024296.
  34. ^ Pauli A, Norris ML, Valen E, Chew GL, Gagnon JA, Zimmerman S, Mitchell A, Ma J, Dubrulle J, Reyon D, Tsai SQ, Joung JK, Saghatelian A, Schier AF (February 2014). "Toddler: an embryonic signal that promotes cell movement via Apelin receptors". Ilm-fan. 343 (6172): 1248636. doi:10.1126/science.1248636. PMC  4107353. PMID  24407481.
  35. ^ Ingolia NT, Lareau LF, Weissman JS (November 2011). "Ribosome profiling of mouse embryonic stem cells reveals the complexity and dynamics of mammalian proteomes". Hujayra. 147 (4): 789–802. doi:10.1016/j.cell.2011.10.002. PMC  3225288. PMID  22056041.
  36. ^ a b Ji Z, Song R, Regev A, Struhl K (December 2015). "Ko'p lncRNA, 5'UTR va pseudogenes tarjima qilingan va ba'zilari funktsional oqsillarni ifoda etishi mumkin". eLife. 4: e08890. doi:10.7554 / eLife.08890. PMC  4739776. PMID  26687005.
  37. ^ Guttman M, Russell P, Ingolia NT, Weissman JS, Lander ES (July 2013). "Ribosome profiling provides evidence that large noncoding RNAs do not encode proteins". Hujayra. 154 (1): 240–251. doi:10.1016/j.cell.2013.06.009. PMC  3756563. PMID  23810193.
  38. ^ Guttman M, Amit I, Garber M, French C, Lin MF, Feldser D, Huarte M, Zuk O, Carey BW, Cassady JP, Cabili MN, Jaenisch R, Mikkelsen TS, Jacks T, Hacohen N, Bernstein BE, Kellis M, Regev A, Rinn JL, Lander ES (March 2009). "Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals". Tabiat. 458 (7235): 223–227. Bibcode:2009Natur.458..223G. doi:10.1038/nature07672. PMC  2754849. PMID  19182780.
  39. ^ Ponjavic J, Ponting CP, Lunter G (May 2007). "Functionality or transcriptional noise? Evidence for selection within long noncoding RNAs". Genom tadqiqotlari. 17 (5): 556–565. doi:10.1101/gr.6036807. PMC  1855172. PMID  17387145.
  40. ^ Haerty W, Ponting CP (May 2013). "Mutations within lncRNAs are effectively selected against in fruitfly but not in human". Genom biologiyasi. 14 (5): R49. doi:10.1186/gb-2013-14-5-r49. PMC  4053968. PMID  23710818.
  41. ^ Washietl S, Kellis M, Garber M (April 2014). "Evolutionary dynamics and tissue specificity of human long noncoding RNAs in six mammals". Genom tadqiqotlari. 24 (4): 616–628. doi:10.1101/gr.165035.113. PMC  3975061. PMID  24429298.
  42. ^ Kutter C, Watt S, Stefflova K, Wilson MD, Goncalves A, Ponting CP, Odom DT, Marques AC (2012). "Rapid turnover of long noncoding RNAs and the evolution of gene expression". PLOS Genetika. 8 (7): e1002841. doi:10.1371/journal.pgen.1002841. PMC  3406015. PMID  22844254.
  43. ^ Brosius J (2005 yil may). "Waste not, want not—transcript excess in multicellular eukaryotes". Genetika tendentsiyalari. 21 (5): 287–288. doi:10.1016 / j.tig.2005.02.014. PMID  15851065.
  44. ^ Struhl K (February 2007). "Transcriptional noise and the fidelity of initiation by RNA polymerase II". Tabiatning strukturaviy va molekulyar biologiyasi. 14 (2): 103–105. doi:10.1038/nsmb0207-103. PMID  17277804.
  45. ^ Palazzo AF, Lee ES (2015-01-26). "Kodlamaydigan RNK: nima funktsional va keraksiz narsa nima?". Genetika chegaralari. 6: 2. doi:10.3389 / fgene.2015.00002. PMC  4306305. PMID  25674102.
  46. ^ Kapusta A, Feschotte C (October 2014). "Volatile evolution of long noncoding RNA repertoires: mechanisms and biological implications". Genetika tendentsiyalari. 30 (10): 439–452. doi:10.1016/j.tig.2014.08.004. PMC  4464757. PMID  25218058.
  47. ^ Chen J, Shishkin AA, Zhu X, Kadri S, Maza I, Guttman M, Hanna JH, Regev A, Garber M (February 2016). "Evolutionary analysis across mammals reveals distinct classes of long non-coding RNAs". Genom biologiyasi. 17: 19. doi:10.1186/s13059-016-0880-9. PMC  4739325. PMID  26838501.
  48. ^ Ulitsky I (October 2016). "Evolution to the rescue: using comparative genomics to understand long non-coding RNAs". Genetika haqidagi sharhlar. 17 (10): 601–614. doi:10.1038/nrg.2016.85. PMID  27573374.
  49. ^ Hezroni H, Koppstein D, Schwartz MG, Avrutin A, Bartel DP, Ulitsky I (May 2015). "Principles of long noncoding RNA evolution derived from direct comparison of transcriptomes in 17 species". Hujayra hisobotlari. 11 (7): 1110–1122. doi:10.1016/j.celrep.2015.04.023. PMC  4576741. PMID  25959816.
  50. ^ Johnsson P, Lipovich L, Grandér D, Morris KV (March 2014). "Evolutionary conservation of long non-coding RNAs; sequence, structure, function". Biochimica et Biofhysica Acta (BBA) - Umumiy mavzular. 1840 (3): 1063–1071. doi:10.1016/j.bbagen.2013.10.035. PMC  3909678. PMID  24184936.
  51. ^ Rivas E, Clements J, Eddy SR (January 2017). "A statistical test for conserved RNA structure shows lack of evidence for structure in lncRNAs". Tabiat usullari. 14 (1): 45–48. doi:10.1038/nmeth.4066. PMC  5554622. PMID  27819659.
  52. ^ Mercer TR, Dinger ME, Mattick JS (March 2009). "Long non-coding RNAs: insights into functions". Genetika haqidagi sharhlar. 10 (3): 155–159. doi:10.1038/nrg2521. PMID  19188922.
  53. ^ Dinger ME, Amaral PP, Mercer TR, Mattick JS (November 2009). "Pervasive transcription of the eukaryotic genome: functional indices and conceptual implications". Funktsional Genomika va Proteomika bo'yicha brifinglar. 8 (6): 407–423. doi:10.1093/bfgp/elp038. PMID  19770204.
  54. ^ Amaral PP, Clark MB, Gascoigne DK, Dinger ME, Mattick JS (January 2011). "lncRNAdb: uzoq vaqt davomida kodlanmaydigan RNKlar uchun ma'lumot bazasi". Nuklein kislotalarni tadqiq qilish. 39 (Database issue): D146–51. doi:10.1093/nar/gkq1138. PMC  3013714. PMID  21112873.
  55. ^ Quek XC, Thomson DW, Maag JL, Bartonicek N, Signal B, Clark MB, Gloss BS, Dinger ME (January 2015). "lncRNAdb v2.0: funktsional uzun bo'lmagan kodlash RNKlari uchun ma'lumot bazasini kengaytirish". Nuklein kislotalarni tadqiq qilish. 43 (Database issue): D168–73. doi:10.1093 / nar / gku988. PMC  4384040. PMID  25332394.
  56. ^ Ma L, Li A, Zou D, Xu X, Xia L, Yu J, Bajic VB, Zhang Z (January 2015). "LncRNAWiki: harnessing community knowledge in collaborative curation of human long non-coding RNAs". Nuklein kislotalarni tadqiq qilish. 43 (Database issue): D187–92. doi:10.1093/nar/gku1167. PMC  4383965. PMID  25399417.
  57. ^ Smith JE, Alvarez-Dominguez JR, Kline N, Huynh NJ, Geisler S, Hu W, Coller J, Baker KE (June 2014). "Translation of small open reading frames within unannotated RNA transcripts in Saccharomyces cerevisiae". Hujayra hisobotlari. 7 (6): 1858–1866. doi:10.1016/j.celrep.2014.05.023. PMC  4105149. PMID  24931603.
  58. ^ a b Goodrich JA, Kugel JF (August 2006). "Non-coding-RNA regulators of RNA polymerase II transcription". Molekulyar hujayra biologiyasi. 7 (8): 612–616. doi:10.1038/nrm1946. PMID  16723972.
  59. ^ a b Feng J, Bi C, Clark BS, Mady R, Shah P, Kohtz JD (June 2006). "The Evf-2 noncoding RNA is transcribed from the Dlx-5/6 ultraconserved region and functions as a Dlx-2 transcriptional coactivator". Genlar va rivojlanish. 20 (11): 1470–1484. doi:10.1101/gad.1416106. PMC  1475760. PMID  16705037.
  60. ^ Panganiban G, Rubenstein JL (October 2002). "Developmental functions of the Distal-less/Dlx homeobox genes". Rivojlanish. 129 (19): 4371–4386. PMID  12223397.
  61. ^ Pennacchio LA, Ahituv N, Moses AM, Prabhakar S, Nobrega MA, Shoukry M, Minovitsky S, Dubchak I, Holt A, Lewis KD, Plajzer-Frick I, Akiyama J, De Val S, Afzal V, Black BL, Couronne O, Eisen MB, Visel A, Rubin EM (November 2006). "In vivo enhancer analysis of human conserved non-coding sequences". Tabiat. 444 (7118): 499–502. Bibcode:2006Natur.444..499P. doi:10.1038/nature05295. PMID  17086198.
  62. ^ Visel A, Prabhakar S, Akiyama JA, Shoukry M, Lewis KD, Holt A, Plajzer-Frick I, Afzal V, Rubin EM, Pennacchio LA (February 2008). "Ultraconservation identifies a small subset of extremely constrained developmental enhancers". Tabiat genetikasi. 40 (2): 158–160. doi:10.1038/ng.2007.55. PMC  2647775. PMID  18176564.
  63. ^ Pibouin L, Villaudi J, Ferbus D, Myuleris M, Prosperi MT, Remvikos Y, Gubin G (2002 yil fevral). "Yo'g'on ichak karsinomasida ortiqcha ekspresiya mRNKini klonlash-1: yo'g'on ichak karsinomalari kichik qismida haddan tashqari ifoda etilgan ketma-ketlik". Saraton genetikasi va sitogenetikasi. 133 (1): 55–60. doi:10.1016/S0165-4608(01)00634-3. PMID  11890990.
  64. ^ a b v Calin GA, Liu CG, Ferracin M, Hyslop T, Spizzo R, Sevignani C, Fabbri M, Cimmino A, Lee EJ, Wojcik SE, Shimizu M, Tili E, Rossi S, Taccioli C, Pichiorri F, Liu X, Zupo S, Herlea V, Gramantieri L, Lanza G, Alder H, Rassenti L, Volinia S, Schmittgen TD, Kipps TJ, Negrini M, Croce CM (September 2007). "Ultraconserved regions encoding ncRNAs are altered in human leukemias and carcinomas". Saraton xujayrasi. 12 (3): 215–229. doi:10.1016/j.ccr.2007.07.027. PMID  17785203.
  65. ^ Luo S, Lu JY, Liu L, Yin Y, Chen C, Han X, Wu B, Xu R, Liu W, Yan P, Shao W, Lu Z, Li H, Na J, Tang F, Wang J, Zhang YE, Shen X (May 2016). "Divergent lncRNAs Regulate Gene Expression and Lineage Differentiation in Pluripotent Cells". Hujayra ildiz hujayrasi. 18 (5): 637–652. doi:10.1016/j.stem.2016.01.024. PMID  26996597.
  66. ^ Vang X, Arai S, Song X, Reichart D, Du K, Pascual G, Tempst P, Rosenfeld MG, Glass CK, Kurokawa R (iyul 2008). "Induktsiyalangan ncRNAs transkripsiyani inhibe qilish uchun sisdagi RNK bilan bog'langan oqsillarni allosterik ravishda o'zgartiradi". Tabiat. 454 (7200): 126–130. Bibcode:2008Natur.454..126W. doi:10.1038 / nature06992. PMC  2823488. PMID  18509338.
  67. ^ Adelman K, Egan E (March 2017). "Non-coding RNA: More uses for genomic junk". Tabiat. 543 (7644): 183–185. Bibcode:2017Natur.543..183A. doi:10.1038/543183a. PMID  28277509.
  68. ^ Halley P, Kadakkuzha BM, Faghihi MA, Magistri M, Zeier Z, Khorkova O, Coito C, Hsiao J, Lawrence M, Wahlestedt C (January 2014). "Regulation of the apolipoprotein gene cluster by a long noncoding RNA". Hujayra hisobotlari. 6 (1): 222–230. doi:10.1016/j.celrep.2013.12.015. PMC  3924898. PMID  24388749.
  69. ^ Reinius B, Shi C, Hengshuo L, Sandhu KS, Radomska KJ, Rozen GD, Lu L, Kullander K, Uilyams RW, Jazin E (2010 yil noyabr). "Sichqonchada X-inaktivatsiyadan qochib ketadigan domenlarda kodlamaydigan uzoq RNKlarning ayol tomonidan bir tomonlama ifodasi". BMC Genomics. 11: 614. doi:10.1186/1471-2164-11-614. PMC  3091755. PMID  21047393.
  70. ^ Martianov I, Ramadass A, Serra Barros A, Chow N, Akoulitchev A (February 2007). "Repression of the human dihydrofolate reductase gene by a non-coding interfering transcript". Tabiat. 445 (7128): 666–670. doi:10.1038/nature05519. PMID  17237763.
  71. ^ Lee JS, Burkholder GD, Latimer LJ, Haug BL, Braun RP (February 1987). "A monoclonal antibody to triplex DNA binds to eucaryotic chromosomes". Nuklein kislotalarni tadqiq qilish. 15 (3): 1047–1061. doi:10.1093/nar/15.3.1047. PMC  340507. PMID  2434928.
  72. ^ a b Kwek KY, Murphy S, Furger A, Thomas B, O'Gorman W, Kimura H, Proudfoot NJ, Akoulitchev A (November 2002). "U1 snRNA associates with TFIIH and regulates transcriptional initiation". Tabiatning strukturaviy biologiyasi. 9 (11): 800–805. doi:10.1038/nsb862. PMID  12389039.
  73. ^ Yang S, Tutton S, Pierce E, Yoon K (November 2001). "Specific double-stranded RNA interference in undifferentiated mouse embryonic stem cells". Molekulyar va uyali biologiya. 21 (22): 7807–7816. doi:10.1128/MCB.21.22.7807-7816.2001. PMC  99950. PMID  11604515.
  74. ^ Yik JH, Chen R, Nishimura R, Jennings JL, Link AJ, Zhou Q (October 2003). "HEXIM1 va 7SK snRNA ning muvofiqlashtirilgan harakatlari bilan P-TEFb (CDK9 / Cyclin T) kinaz va RNK polimeraza II transkripsiyasini inhibatsiyasi". Molekulyar hujayra. 12 (4): 971–982. doi:10.1016 / S1097-2765 (03) 00388-5. PMID  14580347.
  75. ^ Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J va boshq. (2001 yil fevral). "Inson genomini dastlabki tartiblash va tahlil qilish". Tabiat. 409 (6822): 860–921. Bibcode:2001 yil Natur.409..860L. doi:10.1038/35057062. PMID  11237011.
  76. ^ Waterston RH, Lindblad-Toh K, Birney E, Rogers J, Abril JF, Agarwal P va boshq. (2002 yil dekabr). "Sichqoncha genomining dastlabki ketma-ketligi va qiyosiy tahlili". Tabiat. 420 (6915): 520–562. Bibcode:2002Natur.420..520W. doi:10.1038 / nature01262. PMID  12466850.
  77. ^ Liu WM, Chu WM, Choudary PV, Schmid CW (May 1995). "Cell stress and translational inhibitors transiently increase the abundance of mammalian SINE transcripts". Nuklein kislotalarni tadqiq qilish. 23 (10): 1758–1765. doi:10.1093/nar/23.10.1758. PMC  306933. PMID  7784180.
  78. ^ a b Allen E, Xie Z, Gustafson AM, Sung GH, Spatafora JW, Carrington JC (December 2004). "Evolution of microRNA genes by inverted duplication of target gene sequences in Arabidopsis thaliana". Tabiat genetikasi. 36 (12): 1282–1290. doi:10.1038/ng1478. PMID  15565108.
  79. ^ a b Espinoza, CA, Allen TA, Hieb AR, Kugel JF, Goodrich JA (sentyabr 2004). "B2 RNK to'g'ridan-to'g'ri RNK polimeraza II bilan bog'lanib, transkript sintezini bostiradi". Tabiatning strukturaviy va molekulyar biologiyasi. 11 (9): 822–829. doi:10.1038 / nsmb812. PMID  15300239.
  80. ^ Espinoza CA, Goodrich JA, Kugel JF (April 2007). "Characterization of the structure, function, and mechanism of B2 RNA, an ncRNA repressor of RNA polymerase II transcription". RNK. 13 (4): 583–596. doi:10.1261/rna.310307. PMC  1831867. PMID  17307818.
  81. ^ a b v d e f Mariner PD, Walters RD, Espinoza CA, Drullinger LF, Wagner SD, Kugel JF, Goodrich JA (February 2008). "Human Alu RNA is a modular transacting repressor of mRNA transcription during heat shock". Molekulyar hujayra. 29 (4): 499–509. doi:10.1016/j.molcel.2007.12.013. PMID  18313387.
  82. ^ Shamovsky I, Nudler E (February 2008). "Modular RNA heats up". Molekulyar hujayra. 29 (4): 415–417. doi:10.1016/j.molcel.2008.02.001. PMID  18313380.
  83. ^ Mattick JS (October 2003). "Challenging the dogma: the hidden layer of non-protein-coding RNAs in complex organisms". BioEssays. 25 (10): 930–939. CiteSeerX  10.1.1.476.7561. doi:10.1002/bies.10332. PMID  14505360.
  84. ^ Mohammad F, Pandey RR, Nagano T, Chakalova L, Mondal T, Freyzer P, Kanduri C (iyun 2008). "Kcnq1ot1 / Lit1 kodlamaydigan RNK perinukleolyar mintaqani nishonga olish orqali transkripsiya sukunatiga vositachilik qiladi". Molekulyar va uyali biologiya. 28 (11): 3713–3728. doi:10.1128 / MCB.02263-07. PMC  2423283. PMID  18299392.
  85. ^ Wutz A, Rasmussen TP, Jaenisch R (February 2002). "Chromosomal silencing and localization are mediated by different domains of Xist RNA". Tabiat genetikasi. 30 (2): 167–174. doi:10.1038/ng820. PMID  11780141.
  86. ^ Zearfoss NR, Chan AP, Kloc M, Allen LH, Etkin LD (April 2003). "Identification of new Xlsirt family members in the Xenopus laevis oocyte". Rivojlanish mexanizmlari. 120 (4): 503–509. doi:10.1016/S0925-4773(02)00459-8. PMID  12676327.
  87. ^ Singh K, Carey M, Saragosti S, Botchan M (1985). "Expression of enhanced levels of small RNA polymerase III transcripts encoded by the B2 repeats in simian virus 40-transformed mouse cells". Tabiat. 314 (6011): 553–556. Bibcode:1985Natur.314..553S. doi:10.1038/314553a0. PMID  2581137.
  88. ^ Tang RB, Wang HY, Lu HY, Xiong J, Li HH, Qiu XH, Liu HQ (February 2005). "Increased level of polymerase III transcribed Alu RNA in hepatocellular carcinoma tissue". Molekulyar kanserogenez. 42 (2): 93–96. doi:10.1002/mc.20057. PMID  15593371.
  89. ^ a b Shamovsky I, Nudler E (October 2006). "Gene control by large noncoding RNAs". Science's STKE. 2006 (355): pe40. doi:10.1126/stke.3552006pe40. PMID  17018852.
  90. ^ a b Dieci G, Fiorino G, Castelnuovo M, Teichmann M, Pagano A (December 2007). "The expanding RNA polymerase III transcriptome". Genetika tendentsiyalari. 23 (12): 614–622. doi:10.1016/j.tig.2007.09.001. PMID  17977614.
  91. ^ Pagano JM, Farley BM, McCoig LM, Ryder SP (March 2007). "Molecular basis of RNA recognition by the embryonic polarity determinant MEX-5". Biologik kimyo jurnali. 282 (12): 8883–8894. doi:10.1074/jbc.M700079200. PMID  17264081.
  92. ^ Yoon JH, Abdelmohsen K, Gorospe M (October 2013). "Posttranscriptional gene regulation by long noncoding RNA". The Journal of Molecular Biology. 425 (19): 3723–3730. doi:10.1016/j.jmb.2012.11.024. PMC  3594629. PMID  23178169.
  93. ^ a b Beltran M, Puig I, Peña C, García JM, Alvarez AB, Peña R, Bonilla F, de Herreros AG (March 2008). "Tabiiy antisens transkripsiyasi Snail1 tomonidan epiteliya-mezenximal o'tish paytida Zeb2 / Sip1 genlarining ekspresiyasini tartibga soladi". Genlar va rivojlanish. 22 (6): 756–769. doi:10.1101 / gad.455708. PMC  2275429. PMID  18347095.
  94. ^ Munroe SH, Lazar MA (November 1991). "Inhibition of c-erbA mRNA splicing by a naturally occurring antisense RNA". Biologik kimyo jurnali. 266 (33): 22083–22086. PMID  1657988.
  95. ^ Tiedge H, Chen W, Brosius J (June 1993). "Primary structure, neural-specific expression, and dendritic location of human BC200 RNA". Neuroscience jurnali. 13 (6): 2382–2390. doi:10.1523/JNEUROSCI.13-06-02382.1993. PMC  6576500. PMID  7684772.
  96. ^ Tiedge H, Fremeau RT, Weinstock PH, Arancio O, Brosius J (March 1991). "Dendritic location of neural BC1 RNA". Amerika Qo'shma Shtatlari Milliy Fanlar Akademiyasi materiallari. 88 (6): 2093–2097. Bibcode:1991PNAS...88.2093T. doi:10.1073/pnas.88.6.2093. PMC  51175. PMID  1706516.
  97. ^ Muslimov IA, Banker G, Brosius J, Tiedge H (June 1998). "Activity-dependent regulation of dendritic BC1 RNA in hippocampal neurons in culture". Hujayra biologiyasi jurnali. 141 (7): 1601–1611. doi:10.1083/jcb.141.7.1601. PMC  1828539. PMID  9647652.
  98. ^ Wang H, Iacoangeli A, Lin D, Williams K, Denman RB, Hellen CU, Tiedge H (December 2005). "Dendritic BC1 RNA in translational control mechanisms". Hujayra biologiyasi jurnali. 171 (5): 811–821. doi:10.1083/jcb.200506006. PMC  1828541. PMID  16330711.
  99. ^ Centonze D, Rossi S, Napoli I, Mercaldo V, Lacoux C, Ferrari F, Ciotti MT, De Chiara V, Prosperetti C, Maccarrone M, Fezza F, Calabresi P, Bernardi G, Bagni C (August 2007). "The brain cytoplasmic RNA BC1 regulates dopamine D2 receptor-mediated transmission in the striatum". Neuroscience jurnali. 27 (33): 8885–8892. doi:10.1523/JNEUROSCI.0548-07.2007. PMC  6672174. PMID  17699670.
  100. ^ Lewejohann L, Skryabin BV, Sachser N, Prehn C, Heiduschka P, Thanos S, Jordan U, Dell'Omo G, Vyssotski AL, Pleskacheva MG, Lipp HP, Tiedge H, Brosius J, Prior H (September 2004). "Role of a neuronal small non-messenger RNA: behavioural alterations in BC1 RNA-deleted mice". Xulq-atvorni o'rganish. 154 (1): 273–289. CiteSeerX  10.1.1.572.8071. doi:10.1016/j.bbr.2004.02.015. PMID  15302134.
  101. ^ Golden DE, Gerbasi VR, Sontheimer EJ (August 2008). "An inside job for siRNAs". Molekulyar hujayra. 31 (3): 309–312. doi:10.1016/j.molcel.2008.07.008. PMC  2675693. PMID  18691963.
  102. ^ Czech B, Malone CD, Zhou R, Stark A, Schlingeheyde C, Dus M, Perrimon N, Kellis M, Wohlschlegel JA, Sachidanandam R, Hannon GJ, Brennecke J (June 2008). "An endogenous small interfering RNA pathway in Drosophila". Tabiat. 453 (7196): 798–802. Bibcode:2008Natur.453..798C. doi:10.1038/nature07007. PMC  2895258. PMID  18463631.
  103. ^ a b Ogawa Y, Sun BK, Li JT (iyun 2008). "RNK aralashuvi va X-inaktivatsiya yo'llarining kesishishi". Ilm-fan. 320 (5881): 1336–1341. Bibcode:2008 yil ... 320.1336O. doi:10.1126 / science.1157676. PMC  2584363. PMID  18535243.
  104. ^ Kiefer JC (April 2007). "Epigenetics in development". Rivojlanish dinamikasi. 236 (4): 1144–1156. doi:10.1002/dvdy.21094. PMID  17304537.
  105. ^ a b Mikkelsen TS, Ku M, Jaffe DB, Issac B, Lieberman E, Giannoukos G, Alvarez P, Brockman W, Kim TK, Koche RP, Lee W, Mendenhall E, O'Donovan A, Presser A, Russ C, Xie X, Meissner A, Wernig M, Jaenisch R, Nusbaum C, Lander ES, Bernstein BE (August 2007). "Genome-wide maps of chromatin state in pluripotent and lineage-committed cells". Tabiat. 448 (7153): 553–560. Bibcode:2007Natur.448..553M. doi:10.1038/nature06008. PMC  2921165. PMID  17603471.
  106. ^ Nickerson JA, Krochmalnic G, Wan KM, Penman S (January 1989). "Chromatin architecture and nuclear RNA". Amerika Qo'shma Shtatlari Milliy Fanlar Akademiyasi materiallari. 86 (1): 177–181. Bibcode:1989PNAS...86..177N. doi:10.1073/pnas.86.1.177. PMC  286427. PMID  2911567.
  107. ^ Rodríguez-Campos A, Azorín F (November 2007). "RNA is an integral component of chromatin that contributes to its structural organization". PLOS ONE. 2 (11): e1182. Bibcode:2007PLoSO...2.1182R. doi:10.1371/journal.pone.0001182. PMC  2063516. PMID  18000552.
  108. ^ Chen X, Xu H, Yuan P, Fang F, Huss M, Vega VB, Wong E, Orlov YL, Zhang W, Jiang J, Loh YH, Yeo HC, Yeo ZX, Narang V, Govindarajan KR, Leong B, Shahab A, Ruan Y, Bourque G, Sung WK, Clarke ND, Wei CL, Ng HH (June 2008). "Integration of external signaling pathways with the core transcriptional network in embryonic stem cells". Hujayra. 133 (6): 1106–1117. doi:10.1016/j.cell.2008.04.043. PMID  18555785.
  109. ^ a b v Rinn JL, Kertesz M, Vang JK, Squazzo SL, Xu X, Brugmann SA, Goodnough LH, Helms JA, Farnham PJ, Segal E, Chang HY (2007 yil iyun). "Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs". Hujayra. 129 (7): 1311–1323. doi:10.1016/j.cell.2007.05.022. PMC  2084369. PMID  17604720.
  110. ^ a b Sanchez-Elsner T, Gou D, Kremmer E, Sauer F (February 2006). "Noncoding RNAs of trithorax response elements recruit Drosophila Ash1 to Ultrabithorax". Ilm-fan. 311 (5764): 1118–1123. Bibcode:2006Sci...311.1118S. doi:10.1126/science.1117705. PMID  16497925.
  111. ^ Jia L, Wang Y, Wang C, Du Z, Zhang S, Wen X, Zhang S (2020). "Oplr16 serves as a novel chromatin factor to control stem cell fate by modulating pluripotency-specific chromosomal looping and TET2-mediated DNA demethylation". Nuklein kislotalarni tadqiq qilish. 48 (7): 3935–3948. doi:10.1093/nar/gkaa097. PMC  7144914. PMID  32055844.
  112. ^ Mazo A, Hodgson JW, Petruk S, Sedkov Y, Brock HW (August 2007). "Transcriptional interference: an unexpected layer of complexity in gene regulation". Hujayra fanlari jurnali. 120 (Pt 16): 2755–2761. doi:10.1242/jcs.007633. PMID  17690303.
  113. ^ Denisenko O, Shnyreva M, Suzuki H, Bomsztyk K (October 1998). "Eedning WD40 domenidagi nuqtali mutatsiyalar uning Ezh2 bilan o'zaro ta'sirini bloklaydi". Molekulyar va uyali biologiya. 18 (10): 5634–5642. doi:10.1128 / MCB.18.10.5634. PMC  109149. PMID  9742080.
  114. ^ Katayama S, Tomaru Y, Kasukawa T, Waki K, Nakanishi M, Nakamura M, Nishida H, Yap CC, Suzuki M, Kawai J, Suzuki H, Carninci P, Hayashizaki Y, Wells C, Frith M, Ravasi T, Pang KC, Hallinan J, Mattick J, Hume DA, Lipovich L, Batalov S, Engström PG, Mizuno Y, Faghihi MA, Sandelin A, Chalk AM, Mottagui-Tabar S, Liang Z, Lenhard B, Wahlestedt C (September 2005). "Sutemizuvchilar transkriptomida antisense transkripsiyasi". Ilm-fan. 309 (5740): 1564–1566. Bibcode:2005 yil ... 309.1564R. doi:10.1126 / fan.1112009. PMID  16141073.
  115. ^ a b v Yu W, Gius D, Onyango P, Muldoon-Jacobs K, Karp J, Feinberg AP, Cui H (January 2008). "Epigenetic silencing of tumour suppressor gene p15 by its antisense RNA". Tabiat. 451 (7175): 202–206. Bibcode:2008Natur.451..202Y. doi:10.1038/nature06468. PMC  2743558. PMID  18185590.
  116. ^ Pauler FM, Koerner MV, Barlow DP (June 2007). "Silencing by imprinted noncoding RNAs: is transcription the answer?". Genetika tendentsiyalari. 23 (6): 284–292. doi:10.1016/j.tig.2007.03.018. PMC  2847181. PMID  17445943.
  117. ^ Braidotti G, Baubec T, Pauler F, Seidl C, Smrzka O, Stricker S, Yotova I, Barlow DP (2004). "The Air noncoding RNA: an imprinted cis-silencing transcript". Kantitativ biologiya bo'yicha sovuq bahor porti simpoziumlari. 69: 55–66. doi:10.1101/sqb.2004.69.55. PMC  2847179. PMID  16117633.
  118. ^ Mitsuya K, Meguro M, Li MP, Katoh M, Schulz TC, Kugoh H, Yoshida MA, Niikava N, Feinberg AP, Oshimura M (iyul 1999). "LIT1, monoxromosoma duragaylaridan foydalangan holda differentsial ifoda etilgan transkriptlarni skrining yordamida aniqlangan odamning KvLQT1 joyidagi antisenseli RNK". Inson molekulyar genetikasi. 8 (7): 1209–1217. doi:10.1093 / hmg / 8.7.1209. PMID  10369866.
  119. ^ Manchini-Dinardo D, Stil SJ, Levorse JM, Ingram RS, Tilg'man SM (may 2006). "Kcnq1ot1 transkriptining uzaytirilishi qo'shni genlarning genomik izi uchun zarur". Genlar va rivojlanish. 20 (10): 1268–1282. doi:10.1101 / gad.1416906. PMC  1472902. PMID  16702402.
  120. ^ a b Umlauf D, Goto Y, Cao R, Cerqueira F, Wagschal A, Zhang Y, Feil R (December 2004). "Imprinting along the Kcnq1 domain on mouse chromosome 7 involves repressive histone methylation and recruitment of Polycomb group complexes". Tabiat genetikasi. 36 (12): 1296–1300. doi:10.1038/ng1467. PMID  15516932.
  121. ^ Sleutels F, Zwart R, Barlow DP (February 2002). "The non-coding Air RNA is required for silencing autosomal imprinted genes". Tabiat. 415 (6873): 810–813. Bibcode:2002Natur.415..810S. doi:10.1038/415810a. PMID  11845212.
  122. ^ Zwart R, Sleutels F, Wutz A, Schinkel AH, Barlow DP (September 2001). "Bidirectional action of the Igf2r imprint control element on upstream and downstream imprinted genes". Genlar va rivojlanish. 15 (18): 2361–2366. doi:10.1101/gad.206201. PMC  312779. PMID  11562346.
  123. ^ Fournier C, Goto Y, Ballestar E, Delaval K, Hever AM, Esteller M, Feil R (December 2002). "Allele-specific histone lysine methylation marks regulatory regions at imprinted mouse genes". EMBO jurnali. 21 (23): 6560–6570. doi:10.1093/emboj/cdf655. PMC  136958. PMID  12456662.
  124. ^ a b Wutz A, Gribnau J (October 2007). "X inactivation Xplained". Genetika va rivojlanishning dolzarb fikri. 17 (5): 387–393. doi:10.1016/j.gde.2007.08.001. PMID  17869504.
  125. ^ Morey C, Navarro P, Debrand E, Avner P, Rougeulle C, Clerc P (February 2004). "The region 3′ to Xist mediates X chromosome counting and H3 Lys-4 dimethylation within the Xist gene". EMBO jurnali. 23 (3): 594–604. doi:10.1038/sj.emboj.7600071. PMC  1271805. PMID  14749728.
  126. ^ Costanzi C, Pehrson JR (iyun 1998). "Giston makroH2A1 ayol sutemizuvchilarning harakatsiz X xromosomasida to'plangan". Tabiat. 393 (6685): 599–601. Bibcode:1998 yil natur.393..599C. doi:10.1038/31275. PMID  9634239.
  127. ^ Blasco MA (October 2007). "Telomere length, stem cells and aging". Tabiat kimyoviy biologiyasi. 3 (10): 640–649. doi:10.1038/nchembio.2007.38. PMID  17876321.
  128. ^ a b Schoeftner S, Blasco MA (February 2008). "Developmentally regulated transcription of mammalian telomeres by DNA-dependent RNA polymerase II". Tabiat hujayralari biologiyasi. 10 (2): 228–236. doi:10.1038 / ncb1685. PMID  18157120.
  129. ^ a b Azzalin CM, Reichenbach P, Khoriauli L, Giulotto E, Lingner J (November 2007). "Telomeric repeat containing RNA and RNA surveillance factors at mammalian chromosome ends". Ilm-fan. 318 (5851): 798–801. Bibcode:2007Sci...318..798A. doi:10.1126/science.1147182. PMID  17916692.
  130. ^ Donley N, Stoffregen EP, Smith L, Montagna C, Thayer MJ (April 2013). Bartolomei MS (ed.). "Asynchronous replication, mono-allelic expression, and long range Cis-effects of ASAR6". PLOS Genetika. 9 (4): e1003423. doi:10.1371/journal.pgen.1003423. PMC  3617217. PMID  23593023.
  131. ^ Donley N, Smith L, Thayer MJ (January 2015). Bartolomei MS (ed.). "ASAR15, A cis-acting locus that controls chromosome-wide replication timing and stability of human chromosome 15". PLOS Genetika. 11 (1): e1004923. doi:10.1371/journal.pgen.1004923. PMC  4287527. PMID  25569254.
  132. ^ Heskett MB, Smith LG, Spellman P, Thayer MJ (June 2020). "Reciprocal monoallelic expression of ASAR lncRNA genes controls replication timing of human chromosome 6". RNK. 26 (6): 724–738. doi:10.1261/rna.073114.119. PMID  32144193.
  133. ^ Lukiw WJ, Handley P, Wong L, Crapper McLachlan DR (June 1992). "BC200 RNA in normal human neocortex, non-Alzheimer dementia (NAD), and senile dementia of the Alzheimer type (AD)". Neyrokimyoviy tadqiqotlar. 17 (6): 591–597. doi:10.1007/bf00968788. PMID  1603265.
  134. ^ Watson JB, Sutcliffe JG (September 1987). "Primate brain-specific cytoplasmic transcript of the Alu repeat family". Molekulyar va uyali biologiya. 7 (9): 3324–3327. doi:10.1128/MCB.7.9.3324. PMC  367971. PMID  2444875.
  135. ^ a b Zeni PF, Mraz M (Nov 2020). "LncRNAs in adaptive immunity: role in physiological and pathological conditions". RNK biologiyasi. doi:10.1080/15476286.2020.1838783. PMID  33094664.
  136. ^ a b Fu X, Ravindranat L, Tran N, Petroviks G, Srivastava S (mart 2006). "Prostata xos va prostata saratoni bilan bog'liq bo'lgan kodlashmagan gen, PCGEM1 tomonidan apoptozni tartibga solish". DNK va hujayra biologiyasi. 25 (3): 135–141. doi:10.1089 / dna.2006.25.135. PMID  16569192.
  137. ^ Lin R, Maeda S, Liu C, Karin M, Edgington TS (February 2007). "A large noncoding RNA is a marker for murine hepatocellular carcinomas and a spectrum of human carcinomas". Onkogen. 26 (6): 851–858. doi:10.1038/sj.onc.1209846. PMID  16878148.
  138. ^ Reis EM, Nakaya HI, Louro R, Canavez FC, Flatschart AV, Almeida GT, Egidio CM, Paquola AC, Machado AA, Festa F, Yamamoto D, Alvarenga R, da Silva CC, Brito GC, Simon SD, Moreira-Filho CA, Leite KR, Camara-Lopes LH, Campos FS, Gimba E, Vignal GM, El-Dorry H, Sogayar MC, Barcinski MA, da Silva AM, Verjovski-Almeida S (August 2004). "Antisense intronic non-coding RNA levels correlate to the degree of tumor differentiation in prostate cancer". Onkogen. 23 (39): 6684–6692. doi:10.1038/sj.onc.1207880. PMID  15221013.
  139. ^ Eis PS, Tam W, Sun L, Chadburn A, Li Z, Gomez MF, Lund E, Dahlberg JE (March 2005). "Accumulation of miR-155 and BIC RNA in human B cell lymphomas". Amerika Qo'shma Shtatlari Milliy Fanlar Akademiyasi materiallari. 102 (10): 3627–3632. Bibcode:2005PNAS..102.3627E. doi:10.1073/pnas.0500613102. PMC  552785. PMID  15738415.
  140. ^ Li J, Witte DP, Van Dyke T, Askew DS (April 1997). "Expression of the putative proto-oncogene His-1 in normal and neoplastic tissues". Amerika patologiya jurnali. 150 (4): 1297–1305. PMC  1858164. PMID  9094986.
  141. ^ Sonkoly E, Bata-Csorgo Z, Pivarcsi A, Polyanka H, Kenderessy-Szabo A, Molnar G, Szentpali K, Bari L, Megyeri K, Mandi Y, Dobozy A, Kemeny L, Szell M (June 2005). "Psoriazga moyilligi bilan bog'liq bo'lgan kodlamaydigan RNK geni, PRINS" romanini aniqlash va tavsifi " (PDF). Biologik kimyo jurnali. 280 (25): 24159–24167. doi:10.1074 / jbc.M501704200. PMID  15855153.
  142. ^ Ishii N, Ozaki K, Sato H, Mizuno H, Saito S, Takahashi A, Miyamoto Y, Ikegawa S, Kamatani N, Hori M, Saito S, Nakamura Y, Tanaka T (2006). "Miyokard infarkti xavfini tug'diradigan yangi kodlashsiz RNK, MIATni aniqlash". Inson genetikasi jurnali. 51 (12): 1087–1099. doi:10.1007 / s10038-006-0070-9. PMID  17066261.
  143. ^ McPherson R, Pertsemlidis A, Kavaslar N, Stewart A, Roberts R, Cox DR, Hinds DA, Pennacchio LA, Tybjaerg-Hansen A, Folsom AR, Boerwinkle E, Hobbs HH, Cohen JC (iyun 2007). "9-xromosoma bo'yicha umumiy allel, koroner yurak kasalligi bilan bog'liq". Ilm-fan. 316 (5830): 1488–1491. Bibcode:2007 yil ... 316.1488M. doi:10.1126 / science.1142447. PMC  2711874. PMID  17478681.
  144. ^ Pasmant E, Laurendeau I, Eron D, Vidaud M, Vidaud D, Bie I (aprel 2007). "Melanoma-asab tizimidagi o'simta oilasida barcha INK4 / ARF lokusini o'z ichiga olgan mikroblar qatorini yo'q qilishning xarakteristikasi: ANRIL, antisens kodsiz RNK, uning ekspressioni ARF bilan birikadi". Saraton kasalligini o'rganish. 67 (8): 3963–3969. doi:10.1158 / 0008-5472. CAN-06-2004. PMID  17440112.
  145. ^ Broadbent HM, Peden JF, Lorkowski S, Goel A, Ongen H, Green F, Clarke R, Collins R, Franzosi MG, Tognoni G, Seedorf U, Rust S, Eriksson P, Hamsten A, Farrall M, Watkins H (mart 2008 yil ). "Koronar arteriya kasalligi va qandli diabetga moyillik ANRIL joyidagi 9p xromosomadagi aniq, chambarchas bog'langan SNPlar bilan kodlangan". Inson molekulyar genetikasi. 17 (6): 806–814. doi:10.1093 / hmg / ddm352. PMID  18048406.
  146. ^ a b Jarinova O, Styuart AF, Roberts R, Uells G, Lau P, Naing T, Buerki C, Maklin BW, Kuk RC, Parker JS, McPherson R (oktyabr 2009). "9p21.3 xromosomasining koronar arteriya kasalligi xavfi lokusining funktsional tahlili". Arterioskleroz, tromboz va qon tomir biologiyasi. 29 (10): 1671–1677. doi:10.1161 / ATVBAHA.109.189522. PMID  19592466.
  147. ^ Liu Y, Sanoff XK, Cho X, Burd Idoralar, Torrice C, Mohlke KL, Ibrohim JG, Tomas NE, Sharpless NE (Aprel 2009). "INK4 / ARF transkripsiyasi ateroskleroz bilan bog'liq 9p21 xromosoma variantlari bilan bog'liq". PLOS ONE. 4 (4): e5027. Bibcode:2009PLoSO ... 4.5027L. doi:10.1371 / journal.pone.0005027. PMC  2660422. PMID  19343170.
  148. ^ Shirasawa S, Harada H, Furugaki K, Akamizu T, Ishikava N, Ito K, Ito K, Tamai H, Kuma K, Kubota S, Xiratani H, Tsuchiya T, Baba I, Ishikava M, Tanaka M, Sakay K, Aoki M , Yamamoto K, Sasazuki T (2004 yil oktyabr). "B hujayralariga xos antisens transkripti, SAS-ZFAT targ'ibotchisidagi SNPlar qalqonsimon bezning autoimmun kasalligiga moyilligini aniqlaydi". Inson molekulyar genetikasi. 13 (19): 2221–2231. doi:10.1093 / hmg / ddh245. PMID  15294872.
  149. ^ Faghihi MA, Modarresi F, Xalil AM, Vud DE, Sahagan BG, Morgan TE, Finch Idoralar, St Laurent G, Kenny PJ, Wahlestedt C (iyul 2008). "Altsgeymer kasalligida kodlamaydigan RNK ekspressioni ko'tariladi va beta-sekretsiyani tez oziqlantirishni boshqaradi". Tabiat tibbiyoti. 14 (7): 723–730. doi:10.1038 / nm1784. PMC  2826895. PMID  18587408.
  150. ^ Tufarelli C, Stenli JA, Garrik D, Sharpe JA, Ayyub H, Vud WG, Xiggs DR (iyun 2003). "Antisensli RNKning transkripsiyasi odamlarning genetik kasalligining yangi sababi sifatida genlarni susaytirish va metilatsiyaga olib keladi". Tabiat genetikasi. 34 (2): 157–165. doi:10.1038 / ng1157. PMID  12730694.