中国科技核心期刊
CN:31-1600/Q
ISSN:1004-0374
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《生命科学》 2016, 28(5): 539-550
动态RNA甲基化修饰及其调控机制研究进展
孙慧颖1,2#,郝亚娟1,2#,平晓丽1,2,黄春敏1,杨 莹1,孙宝发1,杨运桂1*
(1 中国科学院北京基因组研究所,遗传与发育协同创新中心,中国科学院精准基因组医学
    重点实验室,北京100101;2 中国科学院大学,北京100049)
摘 要:RNA 可以被100 余种化学修饰所修饰。这些化学修饰以甲基化为主,广泛分布于各种类型的RNA 中,如rRNA、tRNA、snRNA、snoRNA 和mRNA 等,其中针对mRNA 内部修饰丰度最高的6- 甲基腺嘌呤(m6A) 的研究最为深入。m6A 修饰酶( 甲基转移酶METTL3/METTL14/WTAP 和去甲基化酶ALKBH5 与FTO) 和结合蛋白YTHDF2、YTHDF1 与YTHDC1 的发现,证明了RNA 甲基化修饰同DNA甲基化修饰一样是动态可逆的,从而将RNA 甲基化修饰由微调控机制提升到表观转录组新层次。而候选m5C 修饰甲基转移酶NSUN 家族蛋白和去甲基化酶TET 蛋白的初步鉴定,丰富了RNA 甲基化修饰表观转录组研究内涵。RNA 甲基化介导的表观转录组学调控和作用已成为RNA 生物学新研究领域。现重点回顾和展望RNA 的m6A 和m5C 甲基化修饰特征及其潜在生物学功能。
 
Dynamics and biological significance of RNA methylations
SUN Hui-Ying1,2#, HAO Ya-Juan1,2#, PING Xiao-Li1,2, HUANG Chun-Min1,
    YANG Ying1, SUN Bao-Fa1, YANG Yun-Gui1*
(1 Key Laboratory of Genomics and Precision Medicine, Collaborative Innovation Center of Genetics and Development, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China; 2 University of Chinese Academy of Sciences, Beijing 100049, China)
Abstract: Over 100 types of chemical modifications have been identified in various types of RNAs including rRNA, tRNA, snRNA, snoRNA and mRNA, among which methylation is most common. The N6-methyl-adenosine (m6A) as the most common and abundant internal modification on mRNA molecules has been widely studied. The recent identification of m6A modifying enzymes including methyltransferase complex METTL3/METTL14/WTAP, two demethylases ALKBH5 and FTO and binding proteins YTHDF2, YTHDF1 and YTHDC1, indicates that RNA methylation is reversible and represents a novel epitranscriptomic mechanism instead of micro-regulation in gene expression control. Identification of candidate m5C modifying enzymes NSUN family proteins and TET proteins further expands RNA methylation-mediated epitranscriptomics. Epitranscriptomics has become a new research frontier in RNA biology. This review summarizes recent progress in RNA m6A and m5C methylations and proposes their potential biological significance.
 
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