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结构洞察转录组中的 N6-甲基腺苷(m6A)修饰。

Structural Insights into N-methyladenosine (mA) Modification in the Transcriptome.

机构信息

National Key Laboratory of Crop Genetic Improvement and National Center of Plant Gene Research, Huazhong Agricultural University, Wuhan 430070, China.

National Key Laboratory of Crop Genetic Improvement and National Center of Plant Gene Research, Huazhong Agricultural University, Wuhan 430070, China.

出版信息

Genomics Proteomics Bioinformatics. 2018 Apr;16(2):85-98. doi: 10.1016/j.gpb.2018.03.001. Epub 2018 Apr 27.

Abstract

More than 100 types of chemical modifications in RNA have been well documented. Recently, several modifications, such as N-methyladenosine (mA), have been detected in mRNA, opening the window into the realm of epitranscriptomics. The mA modification is the most abundant modification in mRNA and non-coding RNA (ncRNA). At the molecular level, mA 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 mA modification is regulated by three classes of proteins generally referred to as the "writer" (adenosine methyltransferase), "eraser" (mA demethylating enzyme), and "reader" (mA-binding protein). The mA 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 mA-dependent manner. In this review, we summarize the structures of the functional proteins that modulate the mA modification, and provide our insights into the mA-mediated gene regulation.

摘要

已有超过 100 种 RNA 的化学修饰被很好地记录下来。最近,在 mRNA 中发现了几种修饰,如 N6-甲基腺苷(m6A),这为研究 RNA 转录后修饰组学(epitranscriptomics)打开了一扇窗。m6A 修饰是 mRNA 和非编码 RNA(ncRNA)中最丰富的修饰。在分子水平上,m6A 影响 mRNA 代谢的几乎所有方面,包括剪接、翻译和稳定性,以及 microRNA(miRNA)成熟,在多种细胞过程中发挥着重要作用。m6A 修饰由三类蛋白调控,通常被称为“writer”(腺苷甲基转移酶)、“eraser”(m6A 去甲基化酶)和“reader”(m6A 结合蛋白)。writer 和 eraser 分别可逆地安装和去除 m6A 修饰。reader 是 YT521-B 同源(YTH)家族蛋白的成员,以 m6A 依赖的方式选择性地结合 RNA 并影响其命运。在这篇综述中,我们总结了调节 m6A 修饰的功能蛋白的结构,并对 m6A 介导的基因调控提出了我们的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3f0/6112310/c8946937bf7c/gr1.jpg

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