动态RNA甲基化修饰及其调控机制研究进展  

Dynamics and biological significance of RNA methylations

作　　者：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] 

机构地区：[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

出　　处：《生命科学》2016年第5期539-550,共12页Chinese Bulletin of Life Sciences

基　　金：国家自然科学基金项目(31430022,31400672)

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r RNA、t RNA、sn RNA、sno RNA和m RNA等,其中针对m RNA内部修饰丰度最高的6-甲基腺嘌呤(m^6A)的研究最为深入。m^6A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m^5C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m^6A和m^5C甲基化修饰特征及其潜在生物学功能。Over 100 types of chemical modifications have been identified in various types of RNAs including r RNA, t RNA, sn RNA, sno RNA and m RNA, among which methylation is most common. The N6-methyl-adenosine（m^6A） as the most common and abundant internal modification on m RNA molecules has been widely studied. The recent identification of m^6A 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 m^5C 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 m^6A and m^5C methylations and proposes their potential biological significance.

关 键 词：6-甲基腺嘌呤(m^6A) 5-甲基胞嘧啶(m^5C) mRNA 非编码RNA 甲基转移酶 去甲基化酶 甲基化结合蛋白 

分 类 号：Q523[生物学—生物化学] Q752