mRNA转录后调控异常在阿尔茨海默病发病机制中的研究进展  

Research progress on post-transcriptional dysregulation of mRNA in pathogenesis of Alzheimer's disease

作　　者：孙静瑶 佟伟民[1] 牛亚梅[1] SUN Jing-yao;TONG Wei-min;NIU Ya-mei(Department of Pathology, Institute of Basic Medical Sciences CAMS,School of Basic Medicine PUMC, Beijing 100005, China)

机构地区：[1]中国医学科学院基础医学研究所北京协和医学院基础学院病理学系,北京100005

出　　处：《基础医学与临床》2021年第5期749-752,共4页Basic and Clinical Medicine

基　　金：中国医学科学院医学与健康科技创新工程(2016I2M1004)。

摘　　要：mRNA在转录合成之后,会经历剪接、出核、翻译或降解等转录后调控模式,这是确保蛋白质合成与功能发挥的重要前提,而脑内mRNA转录后调控异常是导致阿尔茨海默病(AD)发生的原因之一。本文介绍了AD发病过程中APP、MAPT等致病基因的转录后调控异常事件;同时基于表观转录修饰RNA N^(6)-甲基腺嘌呤甲基化(m^(6)A)对RNA代谢的调节作用、以及其上游调控因子在AD中的异常表现,提出m^(6)A介导的转录后调控异常可能是引起AD发病的重要机制之一。Post-transcriptional regulation of mRNA is an essential step from RNA transcription to gene translation,the process includes mRNA splicing,nuclear export,translation,and decay.Post-transcriptional dysregulation in the brain is one of the causal factors of Alzheimer's disease.This review summarizes the dysfunctional post-transcriptional regulation of APP,MAPT and many other risk genes of AD identified so far.Meanwhile,RNA N6-methyladenosine methylation is the most abundant epitranscriptomic mark on mRNA and regulate almost every step in mRNA metabolism.Due to the abnormal expression of m^(6)A regulators and participation in alternative splicing of risk genes in AD,the hypothesis proposes that post-transcriptional dys-regulation mediated by m^(6)A may function as a novel pathogenic factor of AD.

关 键 词：阿尔茨海默病 MRNA 转录后调控 RNA m6A甲基化 

分 类 号：R741.02[医药卫生—神经病学与精神病学]