《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：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: 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.