mRNA甲基化与疾病的研究进展

基础医学与临床 ›› 2021, Vol. 41 ›› Issue (11): 1671-1679.

mRNA甲基化与疾病的研究进展

李冉¹, 郝延磊^2*

1.山东大学齐鲁医学院,山东济南 250100;
2.济宁医学院附属医院神经内科, 山东济宁 272000

收稿日期:2021-04-08 修回日期:2021-07-31 发布日期:2021-10-27
通讯作者: *yanleihao301@live.com
基金资助:
国家自然科学基金(81771360)

Research progress on mRNA methylation and diseases

LI Ran¹, HAO Yan-lei^2*

1. Cheeloo College of Medicine, Shandong University, Jinan 250100;
2. Department of Neurology, the Affiliated Hospital of Jining Medical University, Jining 272000, China

Received:2021-04-08 Revised:2021-07-31 Published:2021-10-27
Contact: *yanleihao301@live.com

摘要/Abstract

摘要： 包含N⁶-甲基腺苷(m⁶A)﹑N⁵-甲基胞苷(m⁵C)和N¹-甲基腺苷(m¹A)等在内的mRNA甲基化修饰占所有mRNA修饰的60%以上,其在mRNA上的分布各不相同。“编码器”“消码器”“读码器”三者参与mRNA甲基化修饰动态可逆的生物学过程,当某一环节出现异常时就会导致肿瘤、病毒感染、代谢、心脏或神经系统等疾病的发生。目前甲基化修饰检测技术繁多,其中应用最为热门的技术就是高通量测序。

关键词: mRNA甲基化, 编码器, 消码器, 读码器, 疾病

Abstract: mRNA methylation modification, including N⁶-methyladenosine (m⁶A), N⁵-methylcytidine (m⁵C) and N¹-methyladenosine (m¹A), etc., represents more than 60% of all mRNA modifications and varies distribution on mRNA. “Writers” “erasers” “readers” participate in the dynamic and reversible biological process of mRNA methylation modification, which can lead to tumor, virus infection, metabolism diseases, heart or nervous system diseases, etc. when abnormalities occur in a certain link. At present, there are many methylation modification detection technologies, among which the most popular one is high-throughput sequencing.

Key words: mRNA methylation, writers, erasers, readers, diseases

中图分类号:

李冉, 郝延磊. mRNA甲基化与疾病的研究进展[J]. 基础医学与临床, 2021, 41(11): 1671-1679.

LI Ran, HAO Yan-lei. Research progress on mRNA methylation and diseases[J]. Basic & Clinical Medicine, 2021, 41(11): 1671-1679.

参考文献

[1]Roignant JY, Soller M. m(6)A in mRNA: an ancient mechanism for fine-tuning gene expression[J]. Trends Genet, 2017,33:380-390.
[2]Zaccara S, Ries RJ, Jaffrey SR. Reading, writing and erasing mRNA methylation[J]. Nat Rev Mol Cell Biol, 2019,20:608-624.
[3]Shen Q, Zhang Q, Shi Y, et al. Tet2 promotes pathogen infection-induced myelopoiesis through mRNA oxidation[J]. Nature, 2018,554:123-127.
[4]Li X, Xiong X, Zhang M, et al. Base-resolution mapping reveals distinct m(1)A methylome in nuclear- and mitochondrial-encoded transcripts[J]. Mol Cell, 2017,68:993-1005.
[5]Dai Q, Moshitch-Moshkovitz S, Han D, et al. Nm-seq maps 2'-O-methylation sites in human mRNA with base precision[J]. Nat Methods, 2017,14:695-698.
[6]Zhang LS, Liu C, Ma H, et al. Transcriptome-wide mapping of internal N(7)-methylguanosine methylome in mammalian mRNA[J]. Mol Cell, 2019,74:1304-1316.
[7]Arango D, Sturgill D, Alhusaini N, et al. Acetylation of cytidine in mRNA promotes translation efficiency[J]. Cell, 2018,175:1872-1886.
[8]Scholler E, Weichmann F, Treiber T, et al. Interactions, localization, and phosphorylation of the m(6)A generating METTL3-METTL14-WTAP complex[J]. RNA, 2018,24:499-512.
[9]Yue Y, Liu J, Cui X, et al. VIRMA mediates preferential m(6)A mRNA methylation in 3′UTR and near stop codon and associates with alternative polyadenylation[J]. Cell Discov, 2018,4:10. doi: 10.1038/s41421-018-0019-0.
[10]Patil DP, Chen CK, Pickering BF, et al. m(6)A RNA methylation promotes XIST-mediated transcriptional repression[J]. Nature, 2016,537:369-373.
[11]Wen J, Lv R, Ma H, et al. Zc3h13 regulates nuclear RNA m(6)A methylation and mouse rmbryonic stem cell self-renewal[J]. Mol Cell, 2018,69:1028-1038.
[12]Darnell RB, Ke S, Darnell JJ. Pre-mRNA processing includes N(6) methylation of adenosine residues that are retained in mRNA exons and the fallacy of “RNA epigenetics”[J]. RNA, 2018,24:262-267.
[13]Mauer J, Luo X, Blanjoie A, et al. Reversible methylation of m(6)Am in the 5' cap controls mRNA stability[J]. Nature, 2017,541:371-375.
[14]Zheng G, Dahl JA, Niu Y, et al. ALKBH5 is a mammalian RNA demethylase that impacts RNA metabolism and mouse fertility[J]. Mol Cell, 2013,49:18-29.
[15]Liao S, Sun H, Xu C. YTH domain: a family of N(6)-methyladenosine (m(6)A) readers[J]. Genomics Proteomics Bioinformatics, 2018,16:99-107.
[16]Geissler R, Simkin A, Floss D, et al. A widespread sequence-specific mRNA decay pathway mediated by hnRNPs A1 and A2/B1[J]. Genes Dev, 2016,30:1070-1085.
[17]Liu N, Zhou K I, Parisien M, et al. N⁶-methyladenosine alters RNA structure to regulate binding of a low-complexity protein[J]. Nucleic Acids Res, 2017,45:6051-6063.
[18]Choi J, Ieong KW, Demirci H, et al. N(6)-methyladenosine in mRNA disrupts tRNA selection and translation-elongation dynamics[J]. Nat Struct Mol Biol, 2016,23:110-115.
[19]Huang H, Weng H, Sun W, et al. Recognition of RNA N(6)-methyladenosine by IGF2BP proteins enhances mRNA stability and translation[J]. Nat Cell Biol, 2018,20:285-295.
[20]Zhang F, Kang Y, Wang M, et al. Fragile X mental retardation protein modulates the stability of its m⁶A-marked messenger RNA targets[J]. Hum Mol Genet, 2018,27:3936-3950.
[21]Wu R, Li A, Sun B, et al. A novel m(6)A reader Prrc2a controls oligodendroglial specification and myelination[J]. Cell Res, 2019,29:23-41.
[22]Zhong H, Tang HF, Kai Y. N⁶-methyladenine RNA modification (m(6)A): an emerging regulator of metabolic diseases[J]. Curr Drug Targets, 2020,21:1056-1067.
[23]Chen XY, Zhang J, Zhu JS. The role of m(6)A RNA methylation in human cancer[J]. Mol Cancer, 2019,18:103. doi: 10.1186/s12943-019-1033-z.
[24]Du K, Zhang L, Lee T, et al. m(6)A RNA methylation controls neural development and is involved in human diseases[J]. Mol Neurobiol, 2019,56:1596-1606.
[25]Batista PJ. The RNA modification N(6)-methyladenosine and its implications in human disease[J]. Genomics Proteomics Bioinformatics, 2017,15:154-163.