m6A修饰对中枢神经系统功能及疾病的影响  

The effects of m6A modification in central nervous system function and disease

作　　者：史佳宾 王大勇 夏晴[1,2,3] 高旭 Jiabin Shi;Dayong Wang;Qing Xia;Xu Gao(Department of Biochemistry and Molecular Biology,Harbin Medical University,Harbin 150081,China;Translational Medicine Research and Cooperation Center of Northern China,Harbin Medical University,Harbin 150081,China;Heilongjiang Academy of Medical Sciences,Harbin 150081,China)

机构地区：[1]哈尔滨医科大学基础医学院生物化学与分子生物学教研室,哈尔滨150081 [2]哈尔滨医科大学北方转化医学研究合作中心,哈尔滨150081 [3]黑龙江省医学科学院,哈尔滨150081

出　　处：《遗传》2020年第12期1156-1167,共12页Hereditas（Beijing)

基　　金：国家自然科学基金项目(编号:81701078,81773165);黑龙江省自然科学基金项目(编号:QC2017090);黑龙江省普通本科高等学校青年创新人才培养计划项目(编号:UNPYSCT-2016190);中国博士后科学基金(面上资助)项目(编号:2016M600261);中国博士后科学基金(特别资助)项目(编号:2018T110317);哈尔滨医科大学校创新科学研究资助项目(编号:2016JCZX37);黑龙江省博士后经费项目(编号:LBH-Z15163)资助。

摘　　要：6-甲基腺嘌呤(N6-methyladenosine,m6A)是一种重要的RNA修饰,参与细胞内mRNA的整个代谢活动,调控基因的表达,调节多种生物过程,在大脑组织中丰度较高。稳定的m6A修饰有助于胚胎大脑发育、记忆力的形成,在维持中枢神经系统的功能中起到重要作用。当m6A修饰水平及相关蛋白表达水平发生改变时,将会引起神经系统功能异常,包括脑组织发育迟缓、轴突再生能力障碍、记忆力改变以及干细胞更新和分化紊乱等。近年来的研究还发现,m6A修饰及其相关蛋白在阿尔茨海默症、帕金森症、脆性X染色体综合征、抑郁症和胶质母细胞瘤等众多神经系统疾病的发展进程中扮演关键角色。本文主要综述了近年来在中枢神经系统中m6A修饰调控机制研究的相关进展,重点介绍了m6A修饰介导的基因表达调控对中枢神经系统生物学功能以及多种相关疾病的影响,以期为中枢神经系统疾病提供新的研究靶点和治疗方向。N6-methyladenosine(m6A)is an important RNA modification,which is highly active in brain tissues participates in global intracellular mRNA metabolism,and regulates gene expression and a variety of biological processes.Stable m6A modification contributes to the normal embryonic brain development and memory formation and plays an important role in maintaining the functions of the central nervous system.However,changes in the level of m6A modification and the expression of its related proteins cause abnormal nervous system functions,including brain tissue development retardation,axon regeneration disorders,memory changes,and stem cell renewal and differentiation disorders.Recent studies have also found that m6A modification and its related proteins play key roles in the development of various nervous system diseases,such as Alzheimer's disease,Parkinson's disease,fragile X-chromosome syndrome,depression and glioblastoma.In this review,we summarize the research progresses of m6A modification regulation mechanism in the central nervous system in recent years,and discusses the effects of gene expression regulation mediated by m6A modification on the biological functions of the central nervous system and related diseases,thereby providing some insights on the new research targets and treatment directions for the central nervous system diseases.

关 键 词：6-甲基腺嘌呤(m6A) 中枢神经系统 干细胞 突触 记忆 

分 类 号：R741[医药卫生—神经病学与精神病学]