Structures of the human pre-catalytic spliceosome and its precursor spliceosome

查看全文 作　　者：Xiechao [1]Zhan;Chuangye [1]Yan;Xiaofeng [1]Zhang;Jianlin [1,2]Lei;Yigong [1,3]Shi

机构地区：[1]Beijing Advanced Innovation Center for Structural Biology, Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences and School of Medicine, Tsinghua University, Beijing 100084, China;[2]Technology Center for Protein Sciences, Ministry of Education Key Laboratory of Protein Sciences,School of Life Sciences, Tsinghua University, Beijing 100084, China;[3]Institute of Biology, Westlake Institute for Advanced Study, Westlake University, 18 Shilongshan Road, Xihu District, Hangzhou, Zhejiang 310024, China

出　　处：《Cell Research》索引2018年第28卷第12期,共12页

基　　金：the National Natural Science Foundation of China(31621092 and 31430020). 摘　　要：The pre-catalytic spliceosome (B complex) is preceded by its precursor spliceosome (pre-B complex) and followed by the activated spliceosome (Bact complex). The pre-B-to-B and B-to-Bact transitions are driven by the ATPase/helicases Prp28 and Brr2,respectively. In this study,we report the cryo-electron microscopy structures of the human pre-B complex and the human B complex at an average resolution of 5.7 and 3.8 A,respectively. In the pre-B complex,U1 and U2 small nuclear ribonucleoproteins (snRNPs) associate with two edges of the tetrahedron-shaped U4/U6.U5 tri-snRNP. The pre-mRNA is yet to be recognized by U5 or U6 small nuclear RNA (snRNA),and loop I of U5 snRNA remains unengaged. In the B complex,U1 snRNP and Prp28 are dissociated,the 5’-exon is anchored to loop I of U5 snRNA,and the 5’-splice site is recognized by U6 snRNA through duplex formation. In sharp contrast to S. cerevisiae,most components of U2 snRNP and tri-snRNP,exemplified by Brr2,undergo pronounced rearrangements in the human pre-B-to-B transition. Structural analysis reveals mechanistic insights into the assembly and activation of the human spliceosome. 关键词：STRUCTURES HUMAN pre-catalytic SPLICEOSOME ITS PRECURSOR SPLICEOSOME

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Structures of the human pre-catalytic spliceosome and its precursor spliceosome

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