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

Xiaofeng Zhang;Xiechao Zhan;Chuangye Yan;Wenyu Zhang;Dongliang Liu;Jianlin Lei;Yigong Shi

【期刊名称】《细胞研究（英文版）》 【年(卷),期】2019(029)004

【摘要】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 (A),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 conformations,one

with

ILS the

complex

exists

in

two

distinct

one

ATPase/helicase Prp43 and

without.Comparison of these three late-stage human spliceosomes reveals mechanistic insights into exon release and spliceosome disassembly.