《生命科学》 2019, 31(6): 534-543

tRNA 2'-O-甲基化修饰及其修饰酶的生物学功能

李　静1，2，刘如娟1，2*，王恩多1，2，3*

(1 中国科学院上海生物化学与细胞生物学研究所，分子细胞科学卓越创新中心，分子生物学国家重点实验室， 上海 200031；2 中国科学院大学，北京 100864；3 上海科技大学生命科学与技术学院，上海 201210)

摘　要：摘　要：转移核糖核酸(transfer RNA， tRNA) 上存在着大量的转录后修饰，对tRNA 发挥其生物学功能具有重要作用。甲基化修饰作为tRNA 修饰中最广泛存在的一种，可以发生在核苷酸的碱基或者2'-O- 核糖(2'-O-甲基化修饰) 上。tRNA 2'-O- 甲基化修饰广泛存在于古细菌、原核生物和真核生物中，并且在tRNA 第4 位、6 位、18 位、32 位、34 位、39 位、44 位、54 位和56 位均被鉴定到。研究表明，tRNA 2'-O- 甲基化修饰参与调控tRNA 的折叠和成熟、影响tRNA 稳定性及反密码子与mRNA 密码子配对的精确性，并与细胞生长、压力应激和免疫调控密切相关。人细胞质tRNA 2'-O- 甲基化修饰缺陷常常与疾病密切相关，并且潜在的tRNA 2'-O- 甲基修饰酶已经成为药物研发的新靶点。开展tRNA 2'-O- 甲基化修饰及其修饰酶的研究将丰富人们对tRNA 2'-O- 甲基化修饰的生物学功能的认识，并为探索tRNA 2'-O- 甲基修饰酶在人类疾病中的致病机制打下基础。现将简要介绍已报道的tRNA 2'-O- 甲基化修饰及其修饰酶的生物学功能。

Biological functions of tRNA 2'-O-methylations and their modifying enzymes

LI Jing1，2， LIU Ru-Juan1，2*， WANG En-Duo1，2，3*

(1 State Key Laboratory of Molecular Biology， CAS Center for Excellence in Molecular Cell Science， Shanghai Institute of Biochemistry and Cell Biology， Chinese Academy of Science， Shanghai 200031， China; 2 University of Chinese Academy of Science， Beijing 100864， China; 3 School of Life Science and Technology， Shanghai Tech University， Shanghai 201210， China)

Abstract: Abstract: Transfer RNAs (tRNAs) contain a variety of post-transcriptional modifications， which play critical roles in the biological functions of tRNAs. Methylation is one of the most frequent tRNA modifications， locating on the
    base group or 2'-O-ribose group of nucleotide. 2'-O-methylations in tRNAs occur in archaea， prokaryotes and eukaryotes， and are identified at position 4， 6， 18， 32， 34， 39， 44， 54 and 56. Accumulating evidence has shown that 2'-O-methylations of tRNAs impact tRNA folding， maturation， stability and the accuracy of the interaction between anticodon and mRNA codon. Moreover， 2'-O-methylations in tRNAs are closely related to cell growth， cellular stress response and immunity. Abnormal pattern of 2'-O-methylations in tRNAs is often correlated with human
    disease， and the putative tRNA 2'-O-methyltransferase has become a new target for drug development. Studies of tRNA 2'-O-methylations and the corresponding modifying enzymes will increase our current understandings of their biological functions， and lay the foundation for exploring the pathogenic mechanisms of the putative tRNA 2'-O-methyltransferases in human diseases. Here， we briefly summarize the latest reports on the biological functions of tRNA 2'-O-methylations and their corresponding modifying enzymes.