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

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.