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

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 structu...

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Veröffentlicht in:Cell research Jg. 29; H. 4; S. 274 - 285
Hauptverfasser: Zhang, Xiaofeng, Zhan, Xiechao, Yan, Chuangye, Zhang, Wenyu, Liu, Dongliang, Lei, Jianlin, Shi, Yigong
Format: Journal Article
Sprache:Englisch
Veröffentlicht: England Nature Publishing Group 01.04.2019
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Adenosine triphosphatase
Adenosine Triphosphatases - metabolism
Catalysis
DEAD-box RNA Helicases - metabolism
Dismantling
DNA helicase
Electron microscopy
Models, Molecular
mRNA
Proteins
Ribonucleic acid
RNA
RNA Helicases - metabolism
RNA Precursors - metabolism
RNA Splicing
RNA Splicing Factors - metabolism
RNA, Small Nuclear - metabolism
snRNA
Spliceosomes
Spliceosomes - metabolism
Splicing
ISSN:1001-0602, 1748-7838, 1748-7838
Online-Zugang:Volltext
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Zusammenfassung: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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ISSN:1001-0602
1748-7838
1748-7838
DOI:10.1038/s41422-019-0143-x