Dynamic m^6A modification and its emerging regulatory role in m RNA splicing  

动态RNAm^6A甲基化修饰及其调控mRNA剪接机制（英文）

作　　者：杨莹 孙宝发 肖文 杨鑫 孙慧颖 赵永良 杨运桂 

机构地区：[1]Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences [2]University of Chinese Academy of Sciences [3]Sino-Danish Center for Science and Education

出　　处：《Science Bulletin》2015年第1期21-32,共12页科学通报（英文版）

基　　金：supported by the National BasicResearch Program of China(2011CB510103,2014CB964902);the National Science Foundation of China(91319308,31430022 and31400672);Strategic Priority Research Program of Chinese Academy ofSciences(XDB14030300)

摘　　要：Recent studies on enzymes regulating dynamic N6-methyl-adenosine （m6A） in RNA together with the findings from m6A-methylated RNA immunoprecipitation followed by high-throughput sequencing （MeRIP-seq/m6A- seq） have revealed a broad biological role of m6A in RNA processing, development, differentiation, metabolism and fertility. RNA m6A methylation is catalyzed by a multi- component methyltransferase complex composed of at least three subunits： METTL3, METTL14 and Wilms tumor 1-associated protein （WTAP）, in which METTL3 and METTL14 serve as catalytic subunits, while WTAP as reg- ulatory subunit. Dioxygenases FTO and ALKBH5, as the first two known m6A demethylases, catalyze m6A removal. Five m6A-binding proteins are classified into cytoplasmic YT521-B homology （YTH） domain-containing family YT- HDF1-3 and nuclear YTHDC1-2. Perturbation of enzy- matic activities catalyzing dynamic m6A results in altered expression of thousands of genes and affects mRNA stability and splicing at the cellular level. Here, we summarize recent discoveries about m6A methyltransferases （writers）,demethylases （erasers） and binding proteins （readers）, and further discuss the potential impacts of m6A on RNA pro- cessing, especially on mRNA splicing.RNA 6-甲基腺嘌呤(m6A)动态修饰酶的研究及RNA m6A免疫沉淀及高通量测序技术(Me RIP-seq/m6A-seq)的快速发展,为揭示m6A在调控RNA加工、个体发育、分化、代谢及生殖等生物学功能提供了新契机.催化m6A修饰形成的甲基转移酶复合物至少包括了催化亚基METTL3和METTL14及调控亚基WTAP;加双氧酶家族蛋白FTO和ALKBH5作为m6A去甲基化酶催化m6A去甲基化;而m6A结合蛋白主要分布于细胞质的YTH结构域家族YTHDF1-3和细胞核的YTHDC1-2.扰动上述调控m6A动态的修饰酶活性可导致上千基因的表达变化,并影响m RNA稳定性及剪接加工等.本文综述了近期m6A甲基转移酶、去甲基化酶和结合蛋白的重要研究进展,并讨论了m6A调控RNA加工代谢尤其是pre-m RNA剪接的潜在作用机制.

关 键 词：N6-Methyl-adenosine （m6A） METHYLTRANSFERASE DEMETHYLASE m6A bindingprotein mRNA splicing 

分 类 号：Q78[生物学—分子生物学]