摘要
RNA剪接是真核生物基因表达过程的关键步骤,由复杂大分子机器剪接体通过精确的分子机制将前体信使RNA(precursor messenger RNA,pre-mRNA)中的内含子去除.该过程在真核生物中保守存在.而复杂真核生物中同时存在U2和U12两类剪接体,其中U2型剪接体负责去除大多数内含子,U12型剪接体负责对一些低频存在的非经典内含子进行剪接.RNA剪接错误及两类剪接体功能紊乱与众多自身免疫疾病、神经退行性疾病、癌症等息息相关.基于数十年生物化学与遗传学研究结合近年来剪接体高分辨率结构解析,U2型剪接体介导的RNA剪接分子作用机制得到系统阐明,U12型稀有剪接体机理研究也取得重要突破.本文将总结以上研究进展,揭示剪接体在运作过程中通过推动RNA分子的构象变化完成RNA剪接过程的核心原理,并对未来研究方向进行展望.
RNA splicing,a key step in eukaryotic gene expression,involves intron removal from pre-mRNA by the spliceosome-a multi-megadalton macromolecular machine-via precise molecular mechanisms.This process is conserved across eukaryotes.In higher eukaryotes,two types of spliceosomes coexist:U2-type(responsible for removing most introns)and U12-type(processing low-abundance non-canonical introns).Abnormal splicing and dysfunction of both spliceosome types are closely linked to numerous diseases,including autoimmune disorders,neurodegenerative diseases,and cancers.Decades of biochemical/genetic studies,combined with recent high-resolution structures of spliceosomes,have systematically elucidated mechanisms of U2-type splicing,with significant breakthroughs also achieved in understanding U12-type spliceosomes.This review summarizes these research advances,reveals the principle of spliceosome-mediated RNA splicing through the promotion of RNA conformational changes,and discusses future research directions.
作者
万蕊雪
WAN RuiXue(Research Center for Industries of the Future(RCIF),Westlake University,Hangzhou 310030,China;Zhejiang Key Laboratory of Structural Biology,School of Life Sciences,Westlake University,Hangzhou 310030,China;Institute of Biology,Westlake Institute for Advanced Study,Hangzhou 310030,China)
出处
《中国科学:生命科学》
北大核心
2025年第8期1542-1556,共15页
Scientia Sinica(Vitae)
基金
国家自然科学基金(批准号:32171214)
浙江省自然科学基金青年原创项目(批准号:LDQ23C050001)资助。
作者简介
联系人:万蕊雪,E-mail:wanruixue@westlake.edu.cn。
