剪接体的结构与分子机理研究  

Structural and mechanistic investigations of the spliceosome

作　　者：施一公[1,2,3,4] Yigong Shi(Beijing Advanced Innovation Center for Structural Biology&Frontier Research Center for Biological Structure,School of Life Sciences,Tsinghua University,Beijing 100084,China;Key Laboratory of Structural Biology of Zhejiang Province,School of Life Sciences,Westlake University,Hangzhou 310024,China;Institute of Biology,Westlake Institute for Advanced Study,Hangzhou 310024,China;Tsinghua University-Peking University Joint Center for Life Sciences,School of Life Sciences,Tsinghua University,Beijing 100084,China)

机构地区：[1]中国科学院 [2]西湖大学 [3]中国科学技术协会第九届全国委员会 [4]清华大学生命科学与医学研究院

出　　处：《科学通报》2020年第27期2952-2953,共2页Chinese Science Bulletin

摘　　要：解析了首个完整剪接体近原子分辨率三维结构,揭示了剪接体组分的组装原则及催化活性中心的分子结构,为理解高等生物的RNA剪接过程提供了重要基础,为进一步探索与剪接异常相关疾病的致病机理和药物开发提供分子基础.Shi’s group has been focusing on the structural and mechanistic elucidation of pre-mRNA splicing in the past decades.After the success of crystal structural elucidation of subcomplexes within spliceosome,they took a direct assault on the intact spliceosome and made the breakthrough in the summer of 2015.They determined the structure of intron lariat spliceosome ILS complex from S.pombe at an average resolution of 3.6Å,which is the first atomic structure of the intact spliceosome,revealing the organization of the spliceosomal components and the conformation of the splicing active site for the first time in the world.Since then,Dr.Shi’s group has reported the high-resolution structures of the spliceosome in all eight major fully-assembled functional states,as well as the structure of the largest pre-assembled subcomplex U4/U6.U5 tri-snRNP from S.cerevisiae.The ten structures give rise to a complete structural view for spliceosome activation,catalysis and disassembly.His group also captured 7 key intermediates of human spliceosome,providing structural basis of the evolution of the spliceosome machinery from lower to higher eukaryotes.Taken together,these accomplishments represent a major contribution in this field,which conceptionally advance our understanding to the molecular mechanism of pre-mRNA splicing and provide unprecedented insights into the research on pathogenesis of related diseases and drug discovery.

关 键 词：剪接体 RNA剪接 高等生物 催化活性中心 三维结构 药物开发 致病机理 分子结构 

分 类 号：Q522[生物学—生物化学]