N^(6)-腺苷甲基化修饰及其对LINE-1的调控机制  

N^(6)-adenosine methylation and the regulatory mechanism on LINE-1

作　　者：张傲 岑山[1] 李晓宇[1] Ao Zhang;Shan Cen;Xiaoyu Li(Department of Immunology,Institute of Medicinal Biotechnology,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100050,China)

机构地区：[1]中国医学科学院&北京协和医学院,医药生物技术研究所免疫生物学室,北京100050

出　　处：《遗传》2024年第3期209-218,共10页Hereditas（Beijing)

基　　金：国家自然科学基金面上项目(编号:31870164)资助。

摘　　要：长散布元件-1(long interspersed elements-1,LINE-1)是现今在人类基因组中唯一具有自主转座能力的转座子,其转座会引起细胞基因组结构和功能的改变,是导致多种严重疾病的重要因素。在转座过程中,LINE-1 mRNA是转座中间体的核心,宿主细胞对其进行相关修饰直接影响转座。N^(6)-腺苷甲基化修饰(m^(6)A)是真核细胞RNA上最丰富且动态可逆的表观遗传修饰。目前发现m^(6)A修饰也存在于LINE-1 mRNA上,参与LINE-1整个生命周期的调控,影响其转座和基因组中LINE-1相邻基因的表达,进而影响基因组稳定性、细胞自我更新与分化潜能,在人类发育和疾病中具有重要作用。本文介绍了LINE-1 m^(6)A修饰的位置、功能以及相关机制,并总结了LINE-1的m^(6)A修饰对其转座调控的研究进展,以期为相关疾病发生发展的机制研究和治疗提供新的思路。Long interspersed elements-1(LINE-1)is the only autonomous transposon in human genome,and its retrotransposition results in change of cellular genome structure and function,leading occurrence of various severe diseases.As a central key intermediated component during life cycle of LINE-1 retrotransposition,the host modification of LINE-1 mRNA affects the LINE-1 transposition directly.N^(6)-adenosine methylation(m^(6)A),the most abundant epigenetic modification on eukaryotic RNA,is dynamically reversible.m^(6)A modification is also found on LINE-1 mRNA,and it participants regulation of the whole LINE-1 replication cycle,with affecting LINE-1 retrotransposition as well as its adjacent genes expression,followed by influencing genomic stability,cellular self-renewal,and differentiation potential,which plays important roles in human development and diseases.In this review,we summarize the research progress in LINE-1 m^(6)A modification,including its modification positions,patterns and related mechanisms,hoping to provide a new sight on the mechanism research and treatment of related diseases.

关 键 词：m^(6)A修饰 逆转录转座子 LINE-1 基因组 基因组稳定性 

分 类 号：R394[医药卫生—医学遗传学]