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N6-甲基腺苷修饰:与新型 RNA 结合蛋白的相互作用及其在信号转导中的作用。

N6-methyladenosine modifications: interactions with novel RNA-binding proteins and roles in signal transduction.

机构信息

a Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province , Sir Run Shaw Hospital, Zhejiang University , Hangzhou , China.

b Department of Anesthesiology and Key Laboratory of Biotherapy of Zhejiang Province , Sir Run Shaw Hospital, Zhejiang University , Hangzhou , China.

出版信息

RNA Biol. 2019 Aug;16(8):991-1000. doi: 10.1080/15476286.2019.1620060. Epub 2019 May 26.

Abstract

RNA epigenetics has received a great deal of attention in recent years, and the reversible N6-methyladenosine (m6A) modification on messenger RNAs (mRNAs) has emerged as a widespread phenomenon. The vital roles of m6A in diverse biological processes are dependent on many RNA-binding proteins (RBPs) with 'reader' or 'nonreader' functions. Moreover, m6A effector proteins affect cellular processes, such as stem cell differentiation, tumor development and the immune response by controlling signal transduction. This review provides an overview of the interactions of m6A with various RBPs, including the 'reader' proteins (excluding the YT521-B homology (YTH) domain proteins and the heterogeneous nuclear ribonucleoproteins (hnRNPs)), and the functional 'nonreader' proteins, and this review focuses on their specific RNA-binding domains and their associations with other m6A effectors. Furthermore, we summarize key m6A-marked targets in distinct signaling pathways, leading to a better understanding of the cellular m6A machinery.

摘要

近年来,RNA 表观遗传学受到了广泛关注,信使 RNA(mRNA)上可逆的 N6-甲基腺苷(m6A)修饰已成为一种广泛存在的现象。m6A 在多种生物过程中的重要作用依赖于具有“读取器”或“非读取器”功能的许多 RNA 结合蛋白(RBPs)。此外,m6A 效应蛋白通过控制信号转导,影响细胞过程,如干细胞分化、肿瘤发生和免疫反应。本综述概述了 m6A 与各种 RBP 的相互作用,包括“读取器”蛋白(不包括 YT521-B 同源(YTH)结构域蛋白和核不均一核糖核蛋白(hnRNPs))和功能“非读取器”蛋白,并重点介绍了它们特定的 RNA 结合结构域及其与其他 m6A 效应蛋白的关联。此外,我们总结了不同信号通路中关键的 m6A 标记靶标,有助于更好地理解细胞内的 m6A 机制。

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