《生命科学》 2023, 35(9): 1169-1176

m6A修饰对神经干细胞分化的影响

杨明思^1,2 , 陈海龙³ , 冀国华³ , 宋　波^1,* , 曲丽娜^3,*

¹大连医科大学病理学与法医学教研室，大连 116041 ²白城医学高等专科学校病理学教研室， 白城 137000 ³中国航天员科研训练中心航天医学基础与应用国家重点实验室，北京 100094

摘　要：

神经干细胞是中枢神经系统中具有自我更新能力并且能够分化产生成熟脑细胞的多潜能细胞，移植神经干细胞治疗神经退行性疾病是一项新兴趋势，已被证实可恢复疾病动物的神经功能。N6- 甲基腺苷(N6-methyladenosine, m6A) 发生在RNA 分子腺苷酸第六位氮原子上，m6A 甲基转移酶(Writers) 和去甲基化酶(Erasers) 能够可逆性调控RNA 分子的m6A 甲基化水平，而m6A 甲基化结合蛋白(Readers) 则可以识别RNA 上的m6A 修饰，影响RNA 的降解、稳定性和翻译等生物学过程。研究表明，m6A 修饰在神经系统中含量丰富，并且随着年龄的增长、疾病的进展，其水平发生改变。m6A 相关酶表达的差异可引起m6A 修饰水平的改变。一些神经相关因子受到m6A 修饰的调控，在不改变碱基序列的条件下影响着神经干细胞的分化和神经系统功能的发挥。现将m6A 修饰对神经干细胞分化的调控作一综述，并进一步展望m6A 修饰对神经系统发育及神经退行性疾病治疗的影响。

通讯作者：宋　波 , Email:bosong@dmu.edu.cn 曲丽娜 , Email:；linaqu@263.net

The effects of m6A modification on differentiation of neural stem cells

YANG Ming-Si^1,2 , CHEN Hai-Long³ , JI Guo-Hua³ , SONG Bo^1,* , QU Li-Na^3,*

¹Department of Pathology and Forensic, Dalian Medical University, Dalian 116041, China ²Department of Pathology, Baicheng Medical College, Baicheng 137000, China ³State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing 100094, China

Abstract:

Neural stem cells are pluripotent cells in the central nervous system that have the ability of self-renewal and can differentiate into mature brain cells. Transplantation of neural stem cells for the treatment of neurodegenerative diseases is a new trend, which has been proved to restore the neural function of diseased animals. N6-methyladenosine (m6A) occurs at the sixth nitrogen atom of adenylate in RNA molecule. m⁶A methyltransferases (Writers) and demethylases (Erasers) can reversibly regulate the level of m6A methylation of RNA molecules, while m6A methylation binding proteins (Readers) can recognize the modification of m6A on RNA and affect biological processes such as RNA degradation, stability and translation. Studies have shown that m⁶A modification is abundant in the nervous system, and its level changes with the growth of age and the progress of disease. The difference in the expression of m6A related enzymes caused the change of m⁶A modification level. Some nerve related factors are regulated by m⁶A modification, which affects the differentiation of neural stem cells and the function of nervous system without changing the base sequence. This article reviews the regulation of m⁶A modification on the differentiation of neural stem cells, and further prospects the impact of m⁶A  modification on the development of nervous system and the treatment of neurodegenerative diseases.

Communication Author：SONG Bo , Email:bosong@dmu.edu.cn QU Li-Na , Email:；linaqu@263.net