2. Academic Validation
  3. Structures of the human spliceosomes before and after release of the ligated exon

Structures of the human spliceosomes before and after release of the ligated exon

  • Cell Res. 2019 Apr;29(4):274-285. doi: 10.1038/s41422-019-0143-x.
Xiaofeng Zhang 1,  Xiechao Zhan 1,  Chuangye Yan 2,  Wenyu Zhang 1,  Dongliang Liu 1,  Jianlin Lei 1 3,  Yigong Shi 4 5
Affiliations

Affiliations

  • 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 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. yancy@mails.tsinghua.edu.cn.
  • 3 Technology Center for Protein Sciences, Ministry of Education Key Laboratory of Protein Sciences, School of Life Sciences, Tsinghua University, Beijing, 100084, China.
  • 4 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. shi-lab@tsinghua.edu.cn.
  • 5 School of Life Sciences, Westlake University, 18 Shilongshan Road, Xihu District, Hangzhou, Zhejiang, 310024, China. shi-lab@tsinghua.edu.cn.
PMID: 30728453 DOI: 10.1038/s41422-019-0143-x
Abstract

Pre-mRNA splicing is executed by the spliceosome, which has eight major functional states each with distinct composition. Five of these eight human spliceosomal complexes, all preceding exon ligation, have been structurally characterized. In this study, we report the cryo-electron microscopy structures of the human post-catalytic spliceosome (P complex) and intron lariat spliceosome (ILS) at average resolutions of 3.0 and 2.9 Å, respectively. In the P complex, the ligated exon remains anchored to loop I of U5 small nuclear RNA, and the 3'-splice site is recognized by the junction between the 5'-splice site and the branch point sequence. The ATPase/helicase Prp22, along with the ligated exon and eight other proteins, are dissociated in the P-to-ILS transition. Intriguingly, the ILS complex exists in two distinct conformations, one with the ATPase/helicase Prp43 and one without. Comparison of these three late-stage human spliceosomes reveals mechanistic insights into exon release and spliceosome disassembly.

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