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Invited Review

RNA epigenetic modification: N6-methyladenosine

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  • 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 date: 2016-02-01

  Revised date: 2016-03-04

  Online published: 2016-04-20

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.

Cite this article

Xiao Zhang, Guifang Jia . RNA epigenetic modification: N6-methyladenosine[J]. Hereditas(Beijing), 2016 , 38(4) : 275 -288 . DOI: 10.16288/j.yczz.16-049

References

[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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