RNA表观遗传修饰：N6-甲基腺嘌呤

doi:10.16288/j.yczz.16-049

遗传 ›› 2016, Vol. 38 ›› Issue (4): 275-288.doi: 10.16288/j.yczz.16-049

• 特邀综述 • 下一篇

RNA表观遗传修饰：N⁶-甲基腺嘌呤

张笑, 贾桂芳

北京大学合成与功能生物分子中心,北京分子科学国家实验室(筹),生物有机与分子工程教育部重点实验室,北京大学化学与分子工程学院化学生物学系,北京 100871

收稿日期:2016-02-01 修回日期:2016-03-04 出版日期:2016-04-20 发布日期:2016-04-20
通讯作者: 贾桂芳,博士,副研究员,研究方向：RNA表观遗传学。E-mail: guifangjia@pku.edu.cn
作者简介:张笑,博士研究生,研究方向：化学生物学。E-mail: zhangxiaoxiao@pku.edu.cn
基金资助:
国家自然科学基金项目（编号：21372022,21210003,21432002）资助[Supported by the National Natural Science Foundation of China (Nos; 21372022, 21210003, 21432002)]

RNA epigenetic modification: N⁶-methyladenosine

Xiao Zhang, Guifang Jia

Synthetic and Functional Biomolecules Center, Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China

Received:2016-02-01 Revised:2016-03-04 Online:2016-04-20 Published:2016-04-20

摘要/Abstract

摘要： N⁶-甲基腺嘌呤(N⁶-methyladenosine, m⁶A)是真核生物信使RNA(Messenger RNA, mRNA)上含量最多的化学修饰之一。类似于DNA和组蛋白化学修饰,m⁶A修饰也同样是动态可逆的,可在时间和空间上被甲基转移酶和去甲基酶调控。哺乳动物体内m⁶A甲基转移酶复合物中有一部分成分已被解析,主要有METTL3 (Methyltransferase-like protein 3)、METTL14 (Methyltransferase-like protein 14)和WTAP (Wilms tumor 1-associating protein)。m⁶A去甲基酶肥胖蛋白FTO (Fat mass and obesity associated protein)和ALKBH5 (AlkB homolog 5)依赖α-酮戊二酸(α-Ketoglutaric acid, α-KG)和Fe(Ⅱ)对m⁶A进行氧化去甲基化反应。m⁶A在生物体内由m⁶A结合蛋白识别,并介导其行使功能。目前发现的m⁶A结合蛋白有YTH结构域蛋白YTHDF1 (YTH domain-containing family protein 1)、YTHDF2 (YTH domain-containing family protein 2)、YTHDC1 (YTH domain-containing protein 1)和核内HNRNPA2B1 (Heterogeneous nuclear ribonucleoproteins A2B1)。本文综述了m⁶A的分布和相关蛋白介导的m⁶A功能研究,以期全面理解m⁶A这一RNA表观遗传新修饰在生命进程中的重要调控作用。

关键词: N6-甲基腺嘌呤(m6A), RNA化学修饰, RNA表观遗传学, 甲基转移酶, 去甲基酶, m6A识别蛋白

Abstract: N⁶-methyladenosine (m⁶A) is one of the most prevalent internal modifications in eukaryotic messenger RNA. The dynamic and reversible modification is installed by methyltransferase complex charactered three subunits: METTL3 (Methyltransferase-like protein 3), METTL14 (Methyltransferase-like protein 14) and WTAP (Wilms tumor 1-associating protein), and erased by two independent demethylases, FTO (Fat mass and obesity associated protein) and ALKBH5 (AlkB homolog 5), in an α-ketoglutarate (α-KG)- and Fe(II)-dependent manner. m⁶A plays funtions in controlling RNA metabolism through the recognition by m⁶A reader proteins, the YTH domain family proteins and HNRNPA2B1 (Heterogeneous nuclear ribonucleoproteins A2B1) . In this review, we summarized distributive features and vital roles of m⁶A and its associated proteins in RNA metabolisms and biological significance, which will help us better understand this new exciting emerging epitranscriptome research field.

Key words: N6-methyladenosine (m6A), RNA chemical modification, epitranscriptome, methyltransferase, demethylase, m6A reader proteins

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.

Xiao Zhang, Guifang Jia. RNA epigenetic modification: N⁶-methyladenosine[J]. HEREDITAS(Beijing), 2016, 38(4): 275-288.

参考文献

[1] Lewis JD, Meehan RR, Henzel WJ, Maurer-Fogy I, Jepp?esen P, Klein F, Bird A. Purification, sequence, and cell?ular localization of a novel chromosomal protein that binds to Methylated DNA. Cell, 1992, 69(6): 905–914.
[2] Bird A. Methylation talk between histones and DNA. Science, 2001, 294(5549): 2113–2115.
[3] Zhang LL, Wu JX. DNA methylation: an epigenetic mechanism for tumorigenesis. Hereditas (Beijing), 2006, 28(7): 880–885.
张丽丽, 吴建新. DNA甲基化——肿瘤产生的一种表观遗传学机制. 遗传, 2006, 28(7): 880–885.
[4] Strahl BD, Allis CD. The language of covalent histone modifications. Nature, 2000, 403(6765): 41–45.
[5] Wang Y, Wysocka J, Perlin J, Leonelli L, Allis C, Coonrod S. Linking covalent histone modifications to epigenetics: the rigidity and plasticity of the marks. Cold Spring Harb Symp Quant Biol, 2004, 69: 161–170.
[6] Maden BEH. The numerous modified nucleotides in euk?aryotic ribosomal RNA. Prog Nucleic Acid Res Mol Biol, 1990, 39: 241–303.
[7] Wang X, Lu ZK, Gomez A, Hon GC, Yue YN, Han DL, Fu Y, Parisien M, Dai Q, Jia GF, Ren B, Pan T, He C. N6-methyladenosine-dependent regulation of messenger RNA stability. Nature, 2014, 505(7481): 117–120.
[8] Wei CM, Gershowitz A, Moss B. Methylated nucleo?tides block 5' terminus of HeLa cell messenger RNA. Cell, 1975, 4(4): 379–386.
[9] Li XY, Xiong XS, Wang K, Wang LX, Shu XT, Ma SQ, Yi CQ. Transcriptome-wide mapping reveals reversible and dynamic N1-methyladenosine methylome. Nat Chem Biol, 2016, doi: 10.1038/nchembio.2040.
[10] 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 GQ, Pan T, Solomon O, Eyal E, Hershkovitz V, Han DL, Doré LC, Amariglio N, Rechavi G, He C. The dynamic N1-methyladenosine met?hylome in eukaryotic messenger RNA. Nature, 2016, 530(7591):
441–446.
[11] Li XY, Zhu P, Ma SQ, Song JH, Bai JY, Sun FF, Yi CQ. Chemical pulldown reveals dynamic pseudouridylation of the mammalian transcriptome. Nat Chem Biol, 2015, 11(8): 592–597.
[12] Dubin DT, Taylor RH. The methylation state of poly A-containing messenger RNA from cultured hamster cells. Nucleic Acids Res, 1975, 2(10): 1653–1668.
[13] Adams JM, Cory S. Modified nucleosides and bizarre 5'- termini in mouse myeloma mRNA. Nature, 1975, 255(5503): 28–33.
[14] Jia GF, Fu Y, Zhao X, Dai Q, Zheng GQ, Yang Y, Yi CQ, Lindahl T, Pan T, Yang YG, He C. N6-methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO. Nat Chem Biol, 2011, 7(12): 885–887.
[15] Fu Y, Dominissini D, Rechavi G, He C. Gene expression regulation mediated through reversible m6A RNA met?hylation. Nat Rev Genet, 2014, 15(5): 293–306.
[16] Delatte B, Wang F, Ngoc LV, Collignon E, Bonvin E, Deplus R, Calonne E, Hassabi B, Putmans P, Awe S, Wetzel C, Kreher J, Soin R, Creppe C, Limbach PA, Gue?ydan C, Kruys V, Brehm A, Minakhina S, Defrance M, Steward R, Fuks F. RNA biochemistry. Transcriptome- wide distribution and function of RNA hydroxymethylcy?tosine. Science, 2016, 351(6270): 282–285.
[17] Tahiliani M, Koh KP, Shen YH, Pastor WA, Bandukwala H, Brudno Y, Agarwal S, Iyer LM, Liu DR, Aravind L, Rao A. Conversion of 5-methylcytosine to 5-hydroxymet?hylcytosine in mammalian DNA by MLL partner TET1. Science, 2009, 324(5929): 930–935.
[18] Ito S, Shen L, Dai Q, Wu SC, Collins LB, Swenberg JA, He C, Zhang Y. Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine. Science, 2011, 333(6047): 1300–1303.
[19] He YF, Li BZ, Li Z, Liu P, Wang Y, Tang QY, Ding JP, Jia YY, Chen ZC, Li L, Sun Y, Li XX, Dai Q, Song CX, Zhang KL, He C, Xu GL. Tet-mediated formation of 5-carbox?ylcytosine and its excision by TDG in mammalian DNA. Science, 2011, 333(6047): 1303–1307.
[20] Agris PF, Vendeix FAP, Grah

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RNA表观遗传修饰：N⁶-甲基腺嘌呤

RNA epigenetic modification: N⁶-methyladenosine

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