mA 修饰调控 mRNA 降解的分子机制。

Molecular Mechanisms Driving mRNA Degradation by mA Modification.

机构信息

Creative Research Initiatives Center for Molecular Biology of Translation, Korea University, Seoul 02841, Republic of Korea; Division of Life Sciences, Korea University, Seoul 02841, Republic of Korea.

Department of Life Science, College of Natural Sciences, Hanyang University, Seoul 04763, Republic of Korea; Research Institute for Natural Sciences, Hanyang University, Seoul 04763, Republic of Korea.

出版信息

Trends Genet. 2020 Mar;36(3):177-188. doi: 10.1016/j.tig.2019.12.007. Epub 2020 Jan 18.

DOI:10.1016/j.tig.2019.12.007

PMID:31964509

Abstract

N-Methyladenosine (mA), the most prevalent internal modification associated with eukaryotic mRNAs, influences many steps of mRNA metabolism, including splicing, export, and translation, as well as stability. Recent studies have revealed that mA-containing mRNAs undergo one of two distinct pathways of rapid degradation: deadenylation via the YT521-B homology (YTH) domain-containing family protein 2 (YTHDF2; an mA reader protein)-CCR4/NOT (deadenylase) complex or endoribonucleolytic cleavage by the YTHDF2-HRSP12-ribonuclease (RNase) P/mitochondrial RNA-processing (MRP) (endoribonuclease) complex. Some mA-containing circular RNAs (circRNAs) are also subject to endoribonucleolytic cleavage by YTHDF2-HRSP12-RNase P/MRP. Here, we highlight recent progress on the molecular mechanisms underlying rapid mRNA degradation via mA and describe our current understanding of the dynamic regulation of mA-mediated mRNA decay through the crosstalk between mA (or YTHDF2) and other cellular factors.

摘要

N6-甲基腺苷（m6A）是真核 mRNA 中最普遍的内部修饰，它影响 mRNA 代谢的许多步骤，包括剪接、输出和翻译以及稳定性。最近的研究表明，含有 m6A 的 mRNA 经历两种截然不同的快速降解途径之一：通过 YT521-B 同源（YTH）结构域蛋白 2（YTHDF2；m6A 阅读蛋白）-CCR4/NOT（脱腺苷酸酶）复合物进行脱腺苷酸化，或通过 YTHDF2-HRSP12-核糖核酸酶（RNase）P/线粒体 RNA 处理（MRP）（内切核酸酶）复合物进行内切核酸酶切割。一些含有 m6A 的环状 RNA（circRNA）也受到 YTHDF2-HRSP12-RNase P/MRP 的内切核酸酶切割。在这里，我们强调了 m6A 介导的快速 mRNA 降解的分子机制的最新进展，并描述了我们目前对 mA（或 YTHDF2）与其他细胞因子之间的相互作用对 mA 介导的 mRNA 衰变的动态调节的理解。