《生命科学》 2022, 34(1): 45-54

mRNA 6-甲基腺嘌呤修饰及其调控蛋白在神经系统中的作用

刘　慧 , 魏　珍 , 曾　燕^*

武汉科技大学脑科学先进技术研究院，武汉 430065

摘　要：

N⁶- 甲基腺嘌呤(N6-methyladenosine, m6A) 作为真核生物中最常见的一种mRNA 甲基化修饰，在神经系统中丰度颇高。随着表观转录组学的兴起，学者们对mRNA m6A 甲基化修饰的研究也在不断深入，发现m6A 甲基化修饰是由甲基转移酶、去甲基化酶以及RNA 结合蛋白共同调控的动态可逆过程。当m6A 调控蛋白表达异常时，m6A 修饰会受其影响，导致mRNA 代谢紊乱、转录和翻译等功能障碍，从而引起神经系统功能异常。该文归纳了mRNA m6A 甲基化修饰的调控蛋白，从它们在神经细胞生长发育、轴突生长和小脑发育等神经系统发育过程中的作用以及与阿尔茨海默病、帕金森病、胶质母细胞瘤等神经系统疾病的关系方面进行了概述。

通讯作者：曾　燕 , Email:zengyan68@wust.edu.cn

The role of mRNA N⁶-methyladenosine methylation modification and its regulatory proteins in nervous system

LIU Hui , WEI Zhen , ZENG Yan^*

Brain Science and Advanced Technology Institute, Wuhan University of Science and Technology, Wuhan 430065, China

Abstract:

As one of the most prevalent internal mRNA modifications in eukaryotes, N6-methyladenosine (m6A) has a high abundance in the nervous system. The understanding of m6A methylation modification is growing, and much evidence suggests that the dynamic and reversible modification of m6A is conducted by three regulatory proteins: methyltransferases, demethylases and m6A binding proteins. The dysregulation of the certain key enzymes and components modified by m6A, influences the m6A modification, leading the mRNA metabolic disorders and molecular dysfunction at transcription and translation levels, which eventually results in the dysfunction of the nervous system. In this present review, the regulatory proteins involved in mRNA m6A methylation are briefly introduced, and their roles in nervous system development processes such as neuralstem cells growth and development, axonal growth and cerebellar development, as well as their relationship with nerve system disease such as Alzheimer’s disease, Parkinson’s disease and glioblastoma are reviewed.

Communication Author：ZENG Yan , Email:zengyan68@wust.edu.cn