m^(6)A修饰对神经干细胞分化的影响  

The effects of m^(6)A modification on differentiation of neural stem cells

作　　者：杨明思 陈海龙[3] 冀国华[3] 宋波[1] 曲丽娜[3] YANG Ming-Si;CHEN Hai-Long;JI Guo-Hua;SONG Bo;QU Li-Na(Department of Pathology and Forensic,Dalian Medical University,Dalian 116041,China;Department of Pathology,Baicheng Medical College,Baicheng 137000,China;State Key Laboratory of Space Medicine Fundamentals and Application,China Astronaut Research and Training Center,Beijing 100094,China)

机构地区：[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

出　　处：《生命科学》2023年第9期1169-1176,共8页Chinese Bulletin of Life Sciences

基　　金：航天医学基础与应用国家重点实验室研究基金资助自主研究项目(SMFA20A01)。

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,m^(6)A)发生在RNA分子腺苷酸第六位氮原子上,m^(6)A甲基转移酶(Writers)和去甲基化酶(Erasers)能够可逆性调控RNA分子的m^(6)A甲基化水平,而m^(6)A甲基化结合蛋白(Readers)则可以识别RNA上的m^(6)A修饰,影响RNA的降解、稳定性和翻译等生物学过程。研究表明,m^(6)A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。m^(6)A相关酶表达的差异可引起m^(6)A修饰水平的改变。一些神经相关因子受到m^(6)A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m^(6)A修饰对神经干细胞分化的调控作一综述,并进一步展望m^(6)A修饰对神经系统发育及神经退行性疾病治疗的影响。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.N^(6)-methyladenosine(m^(6)A)occurs at the sixth nitrogen atom of adenylate in RNA molecule.m^(6)A methyltransferases(Writers)and demethylases(Erasers)can reversibly regulate the level of m^(6)A methylation of RNA molecules,while m^(6)A methylation binding proteins(Readers)can recognize the modification of m^(6)A on RNA and affect biological processes such as RNA degradation,stability and translation.Studies have shown that m^(6)A 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 m^(6)A related enzymes caused the change of m^(6)A modification level.Some nerve related factors are regulated by m^(6)A 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 m^(6)A modification on the differentiation of neural stem cells,and further prospects the impact of m^(6)A modification on the development of nervous system and the treatment of neurodegenerative diseases.

关 键 词：神经干细胞 分化 m^(6)A修饰 甲基转移酶 去甲基化酶 甲基化结合蛋白 

分 类 号：Q189[生物学—神经生物学] R74[生物学—普通生物学]