Structural insights into human exon-defined spliceosome prior to activation  

作　　者：Wenyu Zhang Xiaofeng Zhang Xiechao Zhan Rui Bai Jianlin Lei Chuangye Yan Yigong Shi 

机构地区：[1]Beijing Frontier Research Center for Biological Structure,Tsinghua-Peking Joint Center for Life Sciences,School of Life Sciences,Tsinghua University,Beijing,China [2]Key Laboratory of Structural Biology of Zhejiang Province,School of Life Sciences,Westlake University,Hangzhou,Zhejiang,China [3]Westlake Laboratory of Life Sciences and Biomedicine,Hangzhou,Zhejiang,China [4]Institute of Biology,Westlake Institute for Advanced Study,Hangzhou,Zhejiang,China

出　　处：《Cell Research》2024年第6期428-439,共12页细胞研究（英文版）

基　　金：supported by funds from the National Natural Science Foundation of China(31930059 to Y.S.);the Frontier Research Center for Biological Structure,and start-up funds from Westlake University(to Y.S.).

摘　　要：Spliceosome is often assembled across an exon and undergoes rearrangement to span a neighboring intron.Most states of the intron-defined spliceosome have been structurally characterized.However,the structure of a fully assembled exon-defined spliceosome remains at large.During spliceosome assembly,the pre-catalytic state(B complex)is converted from its precursor(pre-B complex).Here we report atomic structures of the exon-defined human spliceosome in four sequential states:mature pre-B,late pre-B,early B,and mature B.In the previously unknown late pre-B state,U1 snRNP is already released but the remaining proteins are still in the pre-B state;unexpectedly,the RNAs are in the B state,with U6 snRNA forming a duplex with 5′-splice site and U5 snRNA recognizing the 3′-end of the exon.In the early and mature B complexes,the B-specific factors are stepwise recruited and specifically recognize the exon 3′-region.Our study reveals key insights into the assembly of the exon-defined spliceosomes and identifies mechanistic steps of the pre-B-to-B transition.

关 键 词：ACTIVATION INSIGHT STEPWISE 

分 类 号：Q75[生物学—分子生物学]