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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