遗传 ›› 2016, Vol. 38 ›› Issue (4): 275-288.doi: 10.16288/j.yczz.16-049

• 特邀综述 •    下一篇

RNA表观遗传修饰:N6-甲基腺嘌呤

张笑, 贾桂芳   

  1. 北京大学合成与功能生物分子中心,北京分子科学国家实验室(筹),生物有机与分子工程教育部重点实验室,北京大学化学与分子工程学院化学生物学系,北京 100871
  • 收稿日期:2016-02-01 修回日期:2016-03-04 出版日期:2016-04-20 发布日期:2016-04-20
  • 通讯作者: 贾桂芳,博士,副研究员,研究方向:RNA表观遗传学。E-mail: guifangjia@pku.edu.cn
  • 作者简介:张笑,博士研究生,研究方向:化学生物学。E-mail: zhangxiaoxiao@pku.edu.cn
  • 基金资助:
    国家自然科学基金项目(编号:21372022,21210003,21432002)资助[Supported by the National Natural Science Foundation of China (Nos; 21372022, 21210003, 21432002)]

RNA epigenetic modification: N6-methyladenosine

Xiao Zhang, Guifang Jia   

  1. Synthetic and Functional Biomolecules Center, Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China
  • Received:2016-02-01 Revised:2016-03-04 Online:2016-04-20 Published:2016-04-20

摘要: N6-甲基腺嘌呤(N6-methyladenosine, m6A)是真核生物信使RNA(Messenger RNA, mRNA)上含量最多的化学修饰之一。类似于DNA和组蛋白化学修饰,m6A修饰也同样是动态可逆的,可在时间和空间上被甲基转移酶和去甲基酶调控。哺乳动物体内m6A甲基转移酶复合物中有一部分成分已被解析,主要有METTL3 (Methyltransferase-like protein 3)、METTL14 (Methyltransferase-like protein 14)和WTAP (Wilms tumor 1-associating protein)。m6A去甲基酶肥胖蛋白FTO (Fat mass and obesity associated protein)和ALKBH5 (AlkB homolog 5)依赖α-酮戊二酸(α-Ketoglutaric acid, α-KG)和Fe(Ⅱ)对m6A进行氧化去甲基化反应。m6A在生物体内由m6A结合蛋白识别,并介导其行使功能。目前发现的m6A结合蛋白有YTH结构域蛋白YTHDF1 (YTH domain-containing family protein 1)、YTHDF2 (YTH domain-containing family protein 2)、YTHDC1 (YTH domain-containing protein 1)和核内HNRNPA2B1 (Heterogeneous nuclear ribonucleoproteins A2B1)。本文综述了m6A的分布和相关蛋白介导的m6A功能研究,以期全面理解m6A这一RNA表观遗传新修饰在生命进程中的重要调控作用。

关键词: N6-甲基腺嘌呤(m6A), RNA化学修饰, RNA表观遗传学, 甲基转移酶, 去甲基酶, m6A识别蛋白

Abstract: N6-methyladenosine (m6A) is one of the most prevalent internal modifications in eukaryotic messenger RNA. The dynamic and reversible modification is installed by methyltransferase complex charactered three subunits: METTL3 (Methyltransferase-like protein 3), METTL14 (Methyltransferase-like protein 14) and WTAP (Wilms tumor 1-associating protein), and erased by two independent demethylases, FTO (Fat mass and obesity associated protein) and ALKBH5 (AlkB homolog 5), in an α-ketoglutarate (α-KG)- and Fe(II)-dependent manner. m6A plays funtions in controlling RNA metabolism through the recognition by m6A reader proteins, the YTH domain family proteins and HNRNPA2B1 (Heterogeneous nuclear ribonucleoproteins A2B1) . In this review, we summarized distributive features and vital roles of m6A and its associated proteins in RNA metabolisms and biological significance, which will help us better understand this new exciting emerging epitranscriptome research field.

Key words: N6-methyladenosine (m6A), RNA chemical modification, epitranscriptome, methyltransferase, demethylase, m6A reader proteins