RNA甲基化修饰调控和规律

doi:10.16288/j.yczz.18-175

遗传 ›› 2018, Vol. 40 ›› Issue (11): 964-976.doi: 10.16288/j.yczz.18-175

RNA甲基化修饰调控和规律

杨莹^1,^2,³,陈宇晟^1,³,孙宝发^1,^2,³,杨运桂^1,^2,³()

^1. 中国科学院北京基因组研究所,中国科学院精准基因组医学重点实验室,北京 100101
^2. 中国科学院干细胞创新研究院,北京 100101
^3. 中国科学院大学,北京 100049

收稿日期:2018-06-29 修回日期:2018-10-08 出版日期:2018-11-20 发布日期:2018-11-05
通讯作者: 杨运桂 E-mail:ygyang@big.ac.cn
作者简介:杨莹,博士,副研究员,研究方向：RNA表观转录组学。E-mail: yingyang@big.ac.cn
基金资助:
国家重点研发计划项目(973计划)(2016YFC0900300);国家自然科学基金项目(31500659);国家自然科学基金项目(31770872);中国科学院青年创新促进会项目(CAS 2018133)

RNA methylation: regulations and mechanisms

Yang Ying^1,^2,³,Chen Yusheng^1,³,Sun Baofa^1,^2,³,Yang Yungui^1,^2,³()

^1. CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China
^2. Institute of Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China
^3. University of Chinese Academy of Sciences, Beijing 100049, China

Received:2018-06-29 Revised:2018-10-08 Online:2018-11-20 Published:2018-11-05
Contact: Yang Yungui E-mail:ygyang@big.ac.cn
Supported by:
Supported by the Ministry of Science and Technology of China(2016YFC0900300);the National Natural Science Foundation of China(31500659);the National Natural Science Foundation of China(31770872);the Youth Innovation Promotion Association(CAS 2018133)

摘要/Abstract

摘要：

表观遗传学修饰包括DNA、RNA和蛋白质的化学修饰,基于非序列改变所致基因表达和功能水平变化。近年来,在DNA和蛋白质修饰基础上,可逆RNA甲基化修饰研究引领了第3次表观遗传学修饰研究的浪潮。RNA存在100余种化学修饰,甲基化是最主要的修饰形式。鉴定RNA甲基化修饰酶及研发其转录组水平高通量检测技术,是揭示RNA化学修饰调控基因表达和功能规律的基础。本文主要总结了近年来本课题组与合作团队及国内外同行在RNA甲基化表观转录组学研究中取得的主要前沿进展,包括发现了RNA去甲基酶、甲基转移酶和结合蛋白,揭示RNA甲基化修饰调控RNA加工代谢,及其调控正常生理和异常病理等重要生命进程。这些系列研究成果证明RNA甲基化修饰类似于DNA甲基化,具有可逆性,拓展了RNA甲基化表观转录组学研究新领域,完善了中心法则表观遗传学规律。

关键词: 表观转录组学, RNA甲基化, RNA加工, 6-甲基腺嘌呤, 5-甲基胞嘧啶

Abstract:

Epigenetic modifications include the chemical modifications on DNA, RNA and proteins characterized by altered gene expression and function without any changes in the gene sequence. In addition to well-established DNA and protein epigenetic modifications, the reversible RNA methylation has led the third wave of studies in the epigenetic field. RNA has more than 100 chemical modifications, among which methylation is the major type. The identification of catalyzing enzymes for RNA methylation and the development of high-throughput detection technologies for RNA modification at the transcriptomic level are the prerequisites for revealing the regulatory role of RNA methylation in gene expression and biological functions. In this review, we summarize the recent frontier in RNA methylation-mediated epitranscriptomics from our and other laboratories, with emphasis on the discoveries of RNA modification demethylase , methyltransferase and binding protein as well as the illustration of regulatory roles of RNA methylation modification in hematopoietic stem cell differentiation, spermatogenesis, brain development and other pivotal life processes. These findings have shown that RNA methylation is just as reversible as DNA methylation, and opened up a novel field in RNA methylation-mediated epitranscriptomics, which appends a new layer of epigenetic regulation to the central genetic dogma.

Key words: epitranscriptomics, RNA methylation, RNA processing, N ⁶-methyladenosine (m ⁶A), 5-methylcytosine (m ⁵C)

杨莹,陈宇晟,孙宝发,杨运桂. RNA甲基化修饰调控和规律[J]. 遗传, 2018, 40(11): 964-976.

Yang Ying,Chen Yusheng,Sun Baofa,Yang Yungui. RNA methylation: regulations and mechanisms[J]. Hereditas(Beijing), 2018, 40(11): 964-976.

参考文献

[1]	Yang Y, Hsu PJ, Chen YS, Yang YG . Dynamic transcriptomic m 6A decoration: writers, erasers, readers and functions in RNA metabolism . Cell Res, 2018,28(6):616-624.
[2]	Frye M, Harada BT, Behm M, He C . RNA modifications modulate gene expression during development. Science, 2018,361(6409):1346-1349.
[3]	Squires JE, Patel HR, Nousch M, Sibbritt T, Humphreys DT, Parker BJ, Suter CM, Preiss T . Widespread occurrence of 5-methylcytosine in human coding and non-coding RNA. Nucleic Acids Res, 2012,40(11):5023-5033.
[4]	Edelheit S, Schwartz S, Mumbach MR, Wurtzel O, Sorek R . Transcriptome-wide mapping of 5-methylcytidine RNA modifications in bacteria, archaea, and yeast reveals m 5C within archaeal mRNAs . PLoS Genet, 2013,9(6):e1003602.
[5]	Yang X, Yang Y, Sun BF, Chen YS, Xu JW, Lai WY, Li A, Wang X, Bhattarai DP, Xiao W, Sun HY, Zhu Q, Ma HL, Adhikari S, Sun M, Hao YJ, Zhang B, Huang CM, Huang N, Jiang GB, Zhao YL, Wang HL, Sun YP, Yang YG . 5-methylcytosine promotes mRNA export-NSUN2 as the methyltransferase and ALYREF as an m 5C reader . Cell Res, 2017,27(5):606-625.
[6]	David R, Burgess A, Parker B, Li J, Pulsford K, Sibbritt T, Preiss T, Searle IR . Transcriptome-wide mapping of RNA 5-methylcytosine in Arabidopsis mRNAs and noncoding RNAs. Plant Cell, 2017,29(3):445-460.
[7]	Amort T, Rieder D, Wille A, Khokhlova-Cubberley D, Riml C, Trixl L, Jia XY, Micura R, Lusser A . Distinct 5-methylcytosine profiles in poly(A) RNA from mouse embryonic stem cells and brain. Genome Biol, 2017,18(1):1.
[8]	Desrosiers R, Friderici K, Rottman F . Identification of methylated nucleosides in messenger RNA from Novikoff hepatoma cells. Proc Natl Acad Sci USA, 1974,71(10):3971-3975.
[9]	Jia G, Fu Y, Zhao X, Dai Q, Zheng G, Yang Y, Yi C, Lindahl T, Pan T, Yang YG, He C . N 6-methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO. Nat Chem Biol , 2011,7(12):885-887.
[10]	Mauer J, Luo X, Blanjoie A, Jiao X, Grozhik AV, Patil DP, Linder B, Pickering BF, Vasseur JJ, Chen Q, Gross SS, Elemento O, Debart F, Kiledjian M, Jaffrey SR . Reversible methylation of m 6Am in the 5' cap controls mRNA stability . Nature, 2017,541(7637):371-375.
[11]	Wei J, Liu F, Lu Z, Fei Q, Ai Y, He PC, Shi H, Cui X, Su R, Klungland A, Jia G, Chen J, He C . Differential m 6A, m 6Am, and m 1A demethylation mediated by FTO in the cell nucleus and cytoplasm . Mol Cell, 2018,71(6):973-985.
[12]	Su R, Dong L, Li C, Nachtergaele S, Wunderlich M, Qing Y, Deng X, Wang Y, Weng X, Hu C, Yu M, Skibbe J, Dai Q, Zou D, Wu T, Yu K, Weng H, Huang H, Ferchen K, Qin X, Zhang B, Qi J, Sasaki AT, Plas DR, Bradner JE, Wei M, Marcucci G, Jiang X, Mulloy JC, Jin J, He C , Chen J. R-2HG exhibits anti-tumor activity by targeting FTO/ m 6A/MYC/CEBPA signaling. Cell , 2018, 172(1-2):90- 105. e23.
[13]	Zheng G, Dahl JA, Niu Y, Fedorcsak P, Huang CM, Li CJ, Vagbo CB, Shi Y, Wang WL, Song SH, Lu Z, Bosmans RP, Dai Q, Hao YJ, Yang X, Zhao WM, Tong WM, Wang XJ, Bogdan F, Furu K, Fu Y, Jia G, Zhao X, Liu J, Krokan HE, Klungland A, Yang YG, He C . ALKBH5 is a mammalian RNA demethylase that impacts RNA metabolism and mouse fertility. Mol Cell, 2013,49(1):18-29.
[14]	Tuck MT . Partial purification of a 6-methyladenine mRNA methyltransferase which modifies internal adenine residues. Biochem J, 1992,288(Pt1):233-240.
[15]	Bokar JA, Rath-Shambaugh ME, Ludwiczak R, Narayan P, Rottman F . Characterization and partial purification of mRNA N 6-adenosine methyltransferase from HeLa cell nuclei. Internal mRNA methylation requires a multisubunit complex. J Biol Chem , 1994,269(26):17697-17704.
[16]	Bujnicki JM, Feder M, Radlinska M, Blumenthal RM . Structure prediction and phylogenetic analysis of a functionally diverse family of proteins homologous to the MT-A70 subunit of the human mRNA: m 6A methylransferase . J Mol Evol, 2002,55(4):431-444.
[17]	Ping XL, Sun BF, Wang L, Xiao W, Yang X, Wang WJ, Adhikari S, Shi Y, Lv Y, Chen YS, Zhao X, Li A, Yang Y, Dahal U, Lou XM, Liu X, Huang J, Yuan WP, Zhu XF, Cheng T, Zhao YL, Wang X, Rendtlew Danielsen JM, Liu F, Yang YG . Mammalian WTAP is a regulatory subunit of the RNA N 6-methyladenosine methyltransferase. Cell Res , 2014,24(2):177-189.
[18]	Wang Y, Li Y, Toth JI, Petroski MD, Zhang Z, Zhao JC . N 6-methyladenosine modification destabilizes developmental regulators in embryonic stem cells. Nat Cell Biol , 2014,16(2):191-198.
[19]	Liu J, Yue Y, Han D, Wang X, Fu Y, Zhang L, Jia G, Yu M, Lu Z, Deng X, Dai Q, Chen W, He C . A METTL3- METTL14 complex mediates mammalian nuclear RNA N 6-adenosine methylation. Nat Chem Biol , 2014,10(2):93-95.
[20]	Zhong S, Li H, Bodi Z, Button J, Vespa L, Herzog M, Fray RG . MTA is an Arabidopsis messenger RNA adenosine methylase and interacts with a homolog of a sex-specific splicing factor. Plant Cell, 2008,20(5):1278-1288.
[21]	Agarwala SD, Blitzblau HG, Hochwagen A, Fink GR . RNA methylation by the MIS complex regulates a cell fate decision in yeast. Plos Genet, 2012,8(2):e1002732.
[22]	Schwartz S, Mumbach MR, Jovanovic M, Wang T, Maciag K, Bushkin GG, Mertins P, Ter-Ovanesyan D, Habib N, Cacchiarelli D, Sanjana NE, Freinkman E, Pacold ME, Satija R, Mikkelsen TS, Hacohen N, Zhang F, Carr SA, Lander ES, Regev A . Perturbation of m 6A writers reveals two distinct classes of mRNA methylation at Internal and 5' sites . Cell Rep, 2014,8(1):284-296.
[23]	Yue YN, Liu J, Cui XL, Cao J, Luo GZ, Zhang ZH, Cheng T, Gao MS, Shu X, Ma HH, Wang FQ, Wang XX, Shen B, Wang YZ, Feng XH, He C, Liu JZ . VIRMA mediates preferential m 6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation . Cell Discov, 2018,4:10.
[24]	Patil DP, Chen CK, Pickering BF, Chow A, Jackson C, Guttman M , Yang YG.. m 6A RNA methylation promotes XIST-mediated transcriptional repression . Nature, 2016,537(7620):369-373.
[25]	Guo J, Tang HW, Li J, Perrimon N, Yan D . Xio is a component of the Drosophila sex determination pathway and RNA N 6-methyladenosine methyltransferase complex. Proc Natl Acad Sci USA , 2018,115(14):3674-3679.
[26]	Knuckles P, Lence T, Haussmann IU, Jacob D, Kreim N, Carl SH, Masiello I, Hares T, Villaseñor R, Hess D, Andrade-Navarro MA, Biggiogera M, Helm M, Soller M, Bühler M, Roignant JY . Zc3h13/Flacc is required for adenosine methylation by bridging the mRNA-binding factor Rbm15/Spenito to the m 6A machinery component Wtap/Fl(2)d . Genes Dev, 2018,32(5-6):415-429.
[27]	Wen J, Lv R, Ma H, Shen H, He C, Wang J, Jiao F, Liu H, Yang P, Tan L, Lan F, Shi YG, He C, Shi Y , Diao J. Zc3h13 regulates nuclear RNA m 6A methylation and mouse embryonic stem cell self-renewal. Mol Cell, 2018, 69(6): 1028- 1038. e6.
[28]	Pendleton KE, Chen B, Liu K, Hunter OV, Xie Y, Tu BP , Conrad NK. The U6 snRNA m 6A methyltransferase METTL16 regulates SAM synthetase intron retention. Cell , 2017, 169(5): 824- 835. e14.
[29]	Chen T, Hao YJ, Zhang Y, Li MM, Wang M, Han WF, Wu YS, Lv Y, Hao J, Wang LB, Li A, Yang Y, Jin KX, Zhao X, Li YH, Ping XL, Lai WY, Wu LG, Jiang GB, Wang HL, Sang LS, Wang XJ, Yang YG , Yang YG.m 6A RNA methylation is regulated by microRNAs and promotes reprogramming to pluripotency . Cell Stem Cell, 2015,16(3):289-301.
[30]	Perry RP, Kelley DE . Existence of methylated messenger- RNA in mouse L cells. Cell, 1974,1(1):37-42.
[31]	Zhao X, Yang Y, Sun BF, Shi Y, Yang X, Xiao W, Hao YJ, Ping XL, Chen YS, Wang WJ, Jin KX, Wang X, Huang CM, Fu Y, Ge XM, Song SH, Jeong HS, Yanagisawa H, Niu Y, Jia GF, Wu W, Tong WM, Okamoto A, He C, Rendtlew Danielsen JM, Wang XJ, Yang YG . FTO- dependent demethylation of N 6-methyladenosine regulates mRNA splicing and is required for adipogenesis. Cell Res , 2014,24(12):1403-1419.
[32]	Xiao W, Adhikari S, Dahal U, Chen YS, Hao YJ, Sun BF, Sun HY, Li A, Ping XL, Lai WY, Wang X, Ma HL, Huang CM, Yang Y, Huang N, Jiang GB, Wang HL, Zhou Q, Wang XJ, Zhao YL, Yang YG . Nuclear m 6A reader YTHDC1 regulates mRNA splicing . Mol Cell, 2016,61(4):507-519.
[33]	Roundtree IA, Luo GZ, Zhang Z, Wang X, Zhou T, Cui Y, Sha J, Huang X, Guerrero L, Xie P, He E, Shen B , He C . YTHDC1 mediates nuclear export of N 6-methyladenosine methylated mRNAs. eLife , 2017, 6: pii: e31311.
[34]	Alarcón CR, Goodarzi H, Lee H, Liu X, Tavazoie S, Tavazoie SF . HNRNPA2B1 is a mediator of m 6A-dependent nuclear RNA processing events . Cell, 2015,162(6):1299-1308.
[35]	Wu BX, Su SC, Patil DP, Liu HH, Gan JH, Jaffrey SR, Ma JB . Molecular basis for the specific and multivariant recognitions of RNA substrates by human hnRNP A2/B1. Nat Commun, 2018,9:420.
[36]	Liu N, Dai Q, Zheng G, He C, Parisien M, Pan T . N 6-methyladenosine-dependent RNA structural switches regulate RNA-protein interactions. Nature , 2015,518(7540):560-564.
[37]	Liu N, Zhou KI, Parisien M, Dai Q, Diatchenko L, Pan T . N 6-methyladenosine alters RNA structure to regulate binding of a low-complexity protein. Nucleic Acids Res , 2017,45(10):6051-6063.
[38]	Wang X, Lu Z, Gomez A, Hon GC, Yue Y, Han D, Fu Y, Parisien M, Dai Q, Jia G, Ren B, Pan T, He C . N 6-methyladenosine-dependent regulation of messenger RNA stability. Nature , 2014,505(7481):117-120.
[39]	Du H, Zhao Y, He JQ, Zhang Y, Xi HR, Liu MF, Ma JB, Wu LG . YTHDF2 destabilizes m 6A-containing RNA through direct recruitment of the CCR4-NOT deadenylase complex . Nat Commun, 2016,7:12626.
[40]	Wang X, Zhao BS, Roundtree IA, Lu Z, Han D, Ma H, Weng X, Chen K, Shi H, He C . N 6-methyladenosine modulates messenger RNA translation efficiency. Cell , 2015,161(6):1388-1399.
[41]	Li A, Chen YS, Ping XL, Yang X, Xiao W, Yang Y, Sun HY, Zhu Q, Baidya P, Wang X, Bhattarai DP, Zhao YL, Sun BF, Yang YG . Cytoplasmic m 6A reader YTHDF3 promotes mRNA translation . Cell Res, 2017,27(3):444-447.
[42]	Shi H, Wang X, Lu Z, Zhao BS, Ma H, Hsu PJ, Liu C, He C . YTHDF3 facilitates translation and decay of N 6-methyladenosine-modified RNA. Cell Res , 2017,27(3):315-328.
[43]	Hsu PJ, Zhu Y, Ma H, Guo Y, Shi X, Liu Y, Qi M, Lu Z, Shi H, Wang J, Cheng Y, Luo G, Dai Q, Liu M, Guo X, Sha J, Shen B, He C . Ythdc2 is an N 6-methyladenosine binding protein that regulates mammalian spermatogenesis. Cell Res , 2017,27(9):1115-1127.
[44]	Bailey AS, Batista PJ, Gold RS, Chen YG, de Rooij DG, Chang HY , Fuller MT . The conserved RNA helicase YTHDC2 regulates the transition from proliferation to differentiation in the germline . eLife , 2017, 6, pii: e26116.
[45]	Wojtas MN, Pandey RR, Mendel M, Homolka D, Sachidanandam R , Pillai RS.Regulation of m 6A transcripts by the 3°→5° RNA helicase YTHDC2 is essential for a successful meiotic program in the mammalian germline. Mol Cell, 2017, 68(2): 374- 387. e12.
[46]	Jain D, Puno MR, Meydan C, Lailler N, Mason CE, Lima CD, Anderson KV , Keeney S.ketu mutant mice uncover an essential meiotic function for the ancient RNA helicase YTHDC2 . eLife, 2018, 7, pii: e30919.
[47]	Schwartz S, Agarwala SD, Mumbach MR, Jovanovic M, Mertins P, Shishkin A, Tabach Y, Mikkelsen TS, Satija R, Ruvkun G, Carr SA, Lander ES, Fink GR, Regev A . High-resolution mapping reveals a conserved, widespread, dynamic mRNA methylation program in yeast meiosis. Cell, 2013,155(6):1409-1421.
[48]	Zhang S, Zhao BS, Zhou A, Lin K, Zheng S, Lu Z, Chen Y, Sulman EP, Xie K, Bogler O, Majumder S, He C , Huang S. m 6A demethylase ALKBH5 maintains tumorigenicity of glioblastoma stem-like cells by sustaining FOXM1 expression and cell proliferation program. Cancer Cell, 2017, 31(4): 591- 606. e6.
[49]	Hosono Y, Niknafs YS, Prensner JR, Iyer MK, Dhanasekaran SM, Mehra R, Pitchiaya S, Tien J, Escara-Wilke J, Poliakov A, Chu SC, Saleh S, Sankar K, Su F, Guo S, Qiao Y, Freier SM, Bui HH, Cao X, Malik R, Johnson TM, Beer DG, Feng FY, Zhou W , Chinnaiyan AM.Oncogenic role of THOR, a conserved cancer/testis long non-coding RNA. Cell, 2017, 171(7): 1559- 1572. e20.
[50]	Edupuganti RR, Geiger S, Lindeboom RGH, Shi H, Hsu PJ, Lu Z, Wang SY, Baltissen MPA, Jansen P, Rossa M, Muller M, Stunnenberg HG, He C, Carell T, Vermeulen M . N 6-methyladenosine (m 6A) recruits and repels proteins to regulate mRNA homeostasis. Nat Struct Mol Biol , 2017,24(10):870-878.
[51]	Arguello AE DeLiberto AN, Kleiner RE. RNA chemical proteomics reveals the N 6-methyladenosine (m 6A)-regulated protein-RNA interactome. J Am Chem Soc , 2017,139(48):17249-17252.
[52]	Huang H, Weng H, Sun W, Qin X, Shi H, Wu H, Zhao BS, Mesquita A, Liu C, Yuan CL, Hu YC, Huttelmaier S, Skibbe JR, Su R, Deng X, Dong L, Sun M, Li C, Nachtergaele S, Wang Y, Hu C, Ferchen K, Greis KD, Jiang X, Wei M, Qu L, Guan JL, He C, Yang J, Chen J . Recognition of RNAN 6-methyladenosine by IGF2BP proteins enhances mRNA stability and translation. Nat Cell Biol , 2018,20(3):285-295.
[53]	Fustin JM , Doi M,Yamaguchi Y,Hida H,Nishimura S,Yoshida M,Isagawa T,Morioka MS,Kakeya H,Manabe I,Okamura H. RNA-methylation-dependent RNA processing controls the speed of the circadian clock. Cell#, 2013, 155(4): 793-806.
[54]	Xiang Y, Laurent B, Hsu CH, Nachtergaele S, Lu Z, Sheng W, Xu C, Chen H, Ouyang J, Wang S, Ling D, Hsu PH, Zou L, Jambhekar A, He C, Shi Y . RNA m 6A methylation regulates the ultraviolet-induced DNA damage response . Nature, 2017,543(7646):573-576.
[55]	Aguilo F, Zhang F, Sancho A, Fidalgo M, Di Cecilia S, Vashisht A, Lee DF, Chen CH, Rengasamy M, Andino B, Jahouh F, Roman A, Krig SR, Wang R, Zhang W, Wohlschlegel JA, Wang J, Walsh MJ . Coordination of m 6A mRNA methylation and gene transcription by ZFP217 regulates pluripotency and reprogramming . Cell Stem Cell, 2015,17(6):689-704.
[56]	Geula S, Moshitch-Moshkovitz S, Dominissini D, Mansour AA, Kol N, Salmon-Divon M, Hershkovitz V, Peer E, Mor N, Manor YS, Ben-Haim MS, Eyal E, Yunger S, Pinto Y, Jaitin DA, Viukov S, Rais Y, Krupalnik V, Chomsky E, Zerbib M, Maza I, Rechavi Y, Massarwa R, Hanna S, Amit I, Levanon EY, Amariglio N, Stern- Ginossar N, Novershtern N, Rechavi G, Hanna JH . Stem cells. m 6A mRNA methylation facilitates resolution of naive pluripotency toward differentiation . Science, 2015,347(6225):1002-1006.
[57]	Zhao BS, Wang X, Beadell AV, Lu ZK, Shi HL, Kuuspalu A, Ho RK , Yang YG.m 6A-dependent maternal mRNA clearance facilitates zebrafish maternal-to-zygotic transition . Nature, 2017,542(7642):475-478.
[58]	Haussmann IU, Bodi Z, Sanchez-Moran E, Mongan NP, Archer N, Fray RG , Yang YG.m 6A potentiates Sxl alternative pre-mRNA splicing for robust Drosophila sex determination. Nature, 2016,540(7632):301-304.
[59]	Lence T, Akhtar J, Bayer M, Schmid K, Spindler L, Ho CH, Kreim N, Andrade-Navarro MA, Poeck B, Helm M , Yang YG.m 6A modulates neuronal functions and sex determination in Drosophila. Nature, 2016,540(7632):242-247.
[60]	Shen L, Liang Z, Gu X, Chen Y, Teo ZW, Hou X, Cai WM, Dedon PC, Liu L, Yu H . N 6-methyladenosine RNA modification regulates shoot stem cell fate in Arabidopsis. Dev Cell , 2016,38(2):186-200.
[61]	Zhang CX, Chen YS, Sun BF, Wang L, Yang Y, Ma DY, Lv JH, Heng J, Ding YY, Xue YY, Lu XY, Xiao W, Yang YG , Yang YG.m 6A modulates haematopoietic stem and progenitor cell specification . Nature, 2017,549(7671):273-276.
[62]	Lv JH, Zhang YF, Gao SW, Zhang CX, Chen YS, Li W, Yang YG, Zhou Q, Liu F . Endothelial-specific m 6A modulates mouse hematopoietic stem and progenitor cell development via Notch signaling . Cell Res, 2018,28(2):249-252.
[63]	Xu K, Yang Y, Feng GH, Sun BF, Chen JQ, Li YF, Chen YS, Zhang XX, Wang CX, Jiang LY, Liu C, Zhang ZY, Wang XJ, Zhou Q, Yang YG, Li W . Mettl3-mediated m 6A regulates spermatogonial differentiation and meiosis initiation . Cell Res, 2017,27(9):1100-1114.
[64]	Lin Z, Hsu PJ, Xing X, Fang J, Lu Z, Zou Q, Zhang KJ, Zhang X, Zhou Y, Zhang T, Zhang Y, Song W, Jia G, Yang X, He C, Tong MH . Mettl3-/Mettl14-mediated mRNA N 6-methyladenosine modulates murine spermatogenesis. Cell Res , 2017,27(10):1216-1230.
[65]	Li L, Zang L, Zhang F, Chen J, Shen H, Shu L, Liang F, Feng C, Chen D, Tao H, Xu T, Li Z, Kang Y, Wu H, Tang L, Zhang P, Jin P, Shu Q, Li X . Fat mass and obesity- associated (FTO) protein regulates adult neurogenesis. Hum Mol Genet, 2017,26(13):2398-2411.
[66]	Weng YL, Wang X, An R, Cassin J, Vissers C, Liu Y, Liu Y, Xu T, Wang X, Wong SZH, Joseph J, Dore LC, Dong Q, Zheng W, Jin P, Wu H, Shen B, Zhuang X, He C, Liu K, Song H , Ming GL.Epitranscriptomic m 6A regulation of axon regeneration in the adult mammalian nervous system. Neuron , 2018, 97(2): 313- 325. e6.
[67]	Yoon KJ, Ringeling FR, Vissers C, Jacob F, Pokrass M, Jimenez-Cyrus D, Su Y, Kim NS, Zhu Y, Zheng L, Kim S, Wang X, Doré LC, Jin P, Regot S, Zhuang X, Canzar S, He C, Ming GL , Song H.Temporal control of mammalian cortical neurogenesis by m 6A methylation. Cell , 2017, 171(4): 877- 889. e17.
[68]	Li M, Zhao X, Wang W, Shi H, Pan Q, Lu Z, Perez SP, Suganthan R, He C, Bjoras M, Klungland A . Ythdf2-mediated m 6A mRNA clearance modulates neural development in mice . Genome Biol, 2018,19(1):69.
[69]	Ma C, Chang M, Lv H, Zhang ZW, Zhang W, He X, Wu G, Zhao S, Zhang Y, Wang D, Teng X, Liu C, Li Q, Klungland A, Niu Y, Song S, Tong WM . RNA m 6A methylation participates in regulation of postnatal development of the mouse cerebellum . Genome Biol, 2018,19(1):68.
[70]	Wang CX, Cui GS, Liu XY, Xu K, Wang M, Zhang XX, Jiang LY, Li A, Yang Y, Lai WY, Sun BF, Jiang GB, Wang HL, Tong WM, Li W, Wang XJ, Yang YG, Zhou Q . METTL3-mediated m 6A modification is required for cerebellar development . Plos Biol, 2018,16(6):e2004880.
[71]	Ke S, Alemu EA, Mertens C, Gantman EC, Fak JJ, Mele A, Haripal B, Zucker-Scharff I, Moore MJ, Park CY, Vågbø CB, Kusśnierczyk A, Klungland A, Darnell JE , Yang YG.rnell RB. A majority of m 6A residues are in the last exons, allowing the potential for 3' UTR regulation . Genes Dev, 2015,29(19):2037-2053.
[72]	Molinie B, Wang JK, Lim KS, Hillebrand R, Lu ZX, Van Wittenberghe N, Howard BD, Daneshvar K, Mullen AC, Dedon P, Xing Y , Yang YG.. m 6A-LAIC-seq reveals the census and complexity of the m 6A epitranscriptome . Nat Methods, 2016,13(8):692-698.
[73]	Zhou J, Wan J, Gao X, Zhang X, Jaffrey SR, Qian SB . Dynamic m 6A mRNA methylation directs translational control of heat shock response . Nature, 2015,526(7574):591-594.
[74]	Cui XA, Liang Z, Shen LS, Zhang Q, Bao SJ, Geng YK, Zhang B, Leo V, Vardy LA, Lu TG, Gu XF, Yu H . 5-Methylcytosine RNA methylation in Arabidopsis Thaliana. Mol Plant, 2017,10(11):1387-1399.
[75]	Aschenbrenner J, Werner S, Marchand V, Adam M, Motorin Y, Helm M, Marx A . Engineering of a DNA polymerase for direct m 6A sequencing . Angew Chem Int Ed Engl, 2017,57(2):417-421.
[76]	Garalde DR, Snell EA, Jachimowicz D, Sipos B, Lloyd JH, Bruce M, Pantic N, Admassu T, James P, Warland A, Jordan M, Ciccone J, Serra S, Keenan J, Martin S McNeill L, Wallace EJ, Jayasinghe L, Wright C, Blasco J, Young S, Brocklebank D, Juul S, Clarke J, Heron AJ, Turner DJ. Highly parallel direct RNA sequencing on an array of nanopores. Nat Methods, 2018,15(3):201-206.
[77]	Li X, Xiong X, Wang K, Shu X, Ma S, Yi C . Transcriptome-wide mapping reveals reversible and dynamicN 1-methyladenosine methylome. Nat Chem Biol , 2016,12(5):311-316.
[78]	Dominissini D, Nachtergaele S, Moshitch-Moshkovitz S, Peer E, Kol N, Ben-Haim MS, Dai Q, Di Segni A, Salmon-Divon M, Clark WC, Zheng G, Pan T, Solomon O, Eyal E, Hershkovitz V, Han D, Doré LC, Amariglio N, Rechavi G, He C . The dynamic N 1-methyladenosine methylome in eukaryotic messenger RNA. Nature , 2016,530(7591):441-446.
[79]	Li X, Xiong X, Zhang M, Wang K, Chen Y, Zhou J, Mao Y, Lv J, Yi D, Chen XW, Wang C, Qian SB, Yi C . Base-resolution mapping reveals distinct m 1A methylome in nuclear - and mitochondrial-encoded transcripts. Mol Cell , 2017, 68(5): 993- 1005. e9.

编辑推荐

Metrics

www.chinagene.cn
备案号：京ICP备09063187号
总访问:,今日访问:,当前在线:

RNA甲基化修饰调控和规律

RNA methylation: regulations and mechanisms

RichHTML

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 6

编辑推荐

Metrics

[1]	张競文,续倩,李国亮. 癌症发生发展中的表观遗传学研究[J]. 遗传, 2019, 41(7): 567-581.
[2]	王天工, 叶孟. m ⁶A甲基化与肿瘤研究进展[J]. 遗传, 2018, 40(12): 1055-1065.
[3]	张笑, 贾桂芳. RNA表观遗传修饰：N⁶-甲基腺嘌呤[J]. 遗传, 2016, 38(4): 275-288.
[4]	李语丽于军宋述慧. RNA中6-甲基腺嘌呤的研究进展[J]. 遗传, 2013, 35(12): 1340-1351.
[5]	员新旭，冯书堂，潘登科，窦红伟，牟玉莲，李奎 . 小鼠四倍体早期胚胎基因组甲基化模式[J]. 遗传, 2009, 31(4): 387-392.
[6]	韩玉波，张飞雄. RNA聚合酶II中的CTD结构在mRNA转录和加工偶联过程中的重要作用[J]. 遗传, 2003, 25(1): 102-106.