State Key Laboratory of Genetic Engineering, Collaborative Innovation Centre of Genetics and Development, Department of Biochemistry, Institute of Plant Biology, School of Life Sciences, Fudan University, Shanghai 200438, China.
Structural Genomics Consortium, University of Toronto, Toronto, Ontario M5G 1L7, Canada; Department of Physiology, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
Curr Opin Struct Biol. 2017 Dec;47:67-76. doi: 10.1016/j.sbi.2017.05.011. Epub 2017 Jun 16.
N-methyladenosine (mA) as the most prevalent internal modification in mammalian RNAs has been increasingly realized as an important reversible mark that participates in various biological processes and cancer pathogenesis. In this review, we discuss the catalytic mechanisms of MT-A70 domain family proteins for mediating adenosine N-methylation, the removal of this RNA mark by members of ALKB homologue domain family proteins, and the recognition of these mA-modified RNAs by YTH domain family proteins. Our discussions focus on the recent advances in our understandings of the structural and functional properties of N-methyladenosine methyltransferases, demethylases and reader proteins. Overall, we aim to mechanistically explain the reversible and dynamic nature of this unique RNA internal modification that contributes to the complexity of RNA-mediated gene regulation, and inspire new studies in epitranscriptomics.
N6-甲基腺苷（m6A）作为哺乳动物 RNA 中最普遍的内部修饰，已逐渐被认为是参与多种生物学过程和癌症发病机制的重要可逆标记。在这篇综述中，我们讨论了 MT-A70 结构域家族蛋白介导腺苷 N6-甲基化的催化机制、ALKB 同源结构域家族蛋白成员去除这种 RNA 标记的机制，以及 YTH 结构域家族蛋白对这些 m6A 修饰 RNA 的识别。我们的讨论重点是对 N6-甲基腺苷甲基转移酶、去甲基酶和读码蛋白的结构和功能特性的最新认识。总的来说，我们旨在从机制上解释这种独特的 RNA 内部修饰的可逆和动态性质，这种修饰有助于 RNA 介导的基因调控的复杂性，并激发在表观转录组学领域的新研究。
