核内m^(6)A阅读蛋白与选择性剪接在疾病中的研究进展  

Research progress in nuclear m^(6)A reader proteins and alternative splicing in diseases

作　　者：方镜 盛祥利 贾永康 张雷 FANG Jing;SHENG Xiangli;JIA Yongkang;ZHANG Lei(School of Bioengineering and Food,Hubei University of Technology,Wuhan 430068,China)

机构地区：[1]湖北工业大学生物工程与食品学院,湖北武汉430068

出　　处：《生物技术》2024年第4期525-531,共7页Biotechnology

摘　　要：N6-甲基腺苷(m^(6)A)是一种动态可逆的表观调控,是最常见的内部转录后修饰。甲基化酶发生m^(6)A修饰,去甲基化酶擦除修饰,并依赖阅读蛋白对m^(6)A修饰后的RNA的特异性识别。m^(6)A修饰通过招募调节选择性剪接的特定RNA结合蛋白或直接影响RNA结合蛋白与其靶RNA之间的相互作用来调节选择性剪接的模式。m^(6)A修饰扩大了疾病治疗策略的范围,而选择性剪接为m^(6)A阅读蛋白在疾病发生和进展中的机制提供了新见解。该文介绍了m^(6)A阅读蛋白与选择性剪接,全面总结了细胞核内所有的m^(6)A阅读蛋白对信使RNA(messenger RNA,mRNA)的识别和选择性剪接的调控机制,重点阐述了m^(6)A阅读蛋白在多种癌症、流感病毒、白血病等疾病中的生物学功能和作用机制,并探讨m^(6)A依赖性选择性剪接在治疗中的潜在策略。N6-methyladenosine is a dynamic and reversible epigenetic modification,which is the most common internal post-transcriptional modification.Methylation enzymes catalyze m^(6)A modification,while demethylation enzymes remove the modification.The modified RNA is specifically recognized by reader proteins that depend on m^(6)A modification.The m^(6)A modification regulates the pattern of alternative splicing by recruiting RNA-binding proteins that regulate alternative splicing or by directly influencing the interaction between RNA-binding proteins and their target RNA.The m^(6)A modification expands the scope of disease treatment strategies,while alternative splicing provides new insights into the mechanisms of m^(6)A reader proteins in disease occurrence and progression.This article introduces the interaction between m^(6)A reader proteins and alternative splicing,comprehensively summarizes the regulatory mechanisms of all nuclear m^(6)A reader proteins on messenger RNA recognition and alternative splicing,focuses on the biological functions and mechanisms of m^(6)A reader proteins in various diseases such as cancer,influenza virus,and leukemia,and explores the potential strategies of m^(6)A-dependent alternative splicing in treatment.

关 键 词：N6-甲基腺苷 选择性剪接 m^(6)A阅读蛋白 YTHDC1 HNRNPs IGFBPS NKAP 疾病 

分 类 号：R730.2[医药卫生—肿瘤]