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Structural Insights into N6-methyladenosine (m6A) Modification in the Transcriptome

本站小编 Free考研考试/2022-01-03

More than 100 types of chemical modifications in RNA have been well documented. Recently, several modifications, such as N6-methyladenosine (m6A), have been detected in mRNA, opening the window into the realm of epitranscriptomics. The m6A modification is the most abundant modification in mRNA and non-coding RNA (ncRNA). At the molecular level, m6A affects almost all aspects of mRNA metabolism, including splicing, translation, and stability, as well as microRNA (miRNA) maturation, playing essential roles in a range of cellular processes. The m6A modification is regulated by three classes of proteins generally referred to as the “writer” (adenosine methyltransferase), “eraser” (m6A demethylating enzyme), and “reader” (m6A-binding protein). The m6A modification is reversibly installed and removed by writers and erasers, respectively. Readers, which are members of the YT521-B homology (YTH) family proteins, selectively bind to RNA and affect its fate in an m6A-dependent manner. In this review, we summarize the structures of the functional proteins that modulate the m6A modification, and provide our insights into the m6A-mediated gene regulation.
目前在RNA中已经发现有超过100种的化学修饰。最近在真核mRNA上发现一类新修饰,即腺嘌呤甲基化(m6A),拓宽了对表观转录组学(epitranscriptomics)的认识。m6A修饰是在mRNA和非编码RNA(ncRNA)中最丰富的一种修饰。m6A影响mRNA的代谢,包括剪接、翻译和稳定性,以及microRNA的成熟。这些被m6A调节的RNA代谢过程在这一系列的细胞进程中扮演着重要角色。在体内,m6A修饰主要被三类蛋白分子调节,包括催化在RNA甲基化的甲基转移酶,一般被称为“编码器”(writer,m6A甲基转移酶);去除在RNA上甲基化的去甲基化酶,被称为“消码器”(eraser,m6A去甲基化酶);识别RNA上甲基化的蛋白,被称为“读码器”(reader,m6A结合蛋白)。因此,m6A甲基化修饰是个可逆的过程,分别由编码器写入和消码器消除,并且还可以通过读码器识别,参与并影响到一系列的生物学过程。在这篇综述中,我们从结构生物学的角度,系统地总结了这些蛋白或者复合物的结构特征,对调节m6A修饰的分子机理进行了阐述和讨论,为m6A介导的基因表达调控提供了一些见解。





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http://gpb.big.ac.cn/articles/download/636
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