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The m6A Writer: Rise of a Machine for Growing Tasks
Biochemistry ( IF 2.9 ) Pub Date : 2018-12-17 00:00:00 , DOI: 10.1021/acs.biochem.8b01166
Dario L Balacco 1 , Matthias Soller 1
Affiliation  

The central dogma of molecular biology introduced by Crick describes a linear flow of information from DNA to mRNA to protein. Since then it has become evident that RNA undergoes several maturation steps such as capping, splicing, 3′-end processing, and editing. Likewise, nucleotide modifications are common in mRNA and are present in all organisms impacting on the regulation of gene expression. The most abundant modification found in mRNA is N6-methyladenosine (m6A). Deposition of m6A is a nuclear process and is performed by a megadalton writer complex primarily on mRNAs, but also on microRNAs and lncRNAs. The m6A methylosome is composed of the enzymatic core components METTL3 and METTL14, and several auxiliary proteins necessary for its correct positioning and functioning, which are WTAP, VIRMA, FLACC, RBM15, and HAKAI. The m6A epimark is decoded by YTH domain-containing reader proteins YTHDC and YTHDF, but METTLs can act as “readers” as well. Eraser proteins, such as FTO and ALKBH5, can remove the methyl group. Here we review recent progress on the role of m6A in regulating gene expression in light of Crick’s central dogma of molecular biology. In particular, we address the complexity of the writer complex from an evolutionary perspective to obtain insights into the mechanism of ancient m6A methylation and its regulation.

中文翻译:

m6A Writer:用于不断增长的任务的机器的兴起

克里克引入的分子生物学中心法则描述了从 DNA 到 mRNA 再到蛋白质的线性信息流。从那时起,很明显 RNA 经历了几个成熟步骤,例如加帽、剪接、3' 端加工和编辑。同样,核苷酸修饰在 mRNA 中很常见,并且存在于所有影响基因表达调控的生物体中。在 mRNA 中发现的最丰富的修饰是 N6-甲基腺苷 (m 6 A)。m 6 A 的沉积是一个核过程,主要由百万道尔顿 writer 复合物在 mRNA 上进行,但也在 microRNA 和 lncRNA 上进行。米6甲基小体由酶核心成分 METTL3 和 METTL14 以及其正确定位和功能所必需的几种辅助蛋白组成,它们是 WTAP、VIRMA、FLACC、RBM15 和 HAKAI。m 6 A 标记由包含 YTH 域的阅读器蛋白 YTHDC 和 YTHDF 解码,但 METTL 也可以充当“阅读器”。橡皮擦蛋白,如 FTO 和 ALKBH5,可以去除甲基。在这里,我们根据克里克的分子生物学中心法则回顾了 m 6 A 在调节基因表达中的作用的最新进展。特别是,我们从进化的角度解决了 writer 复合物的复杂性,以深入了解古代 m 6 A 甲基化的机制及其调控。
更新日期:2018-12-17
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