biostudies-literature00390Liu SNIH Office of the DirectorNIAID NIH HHSNIGMS NIH HHSNIH HHS1278-1283https://www.ebi.ac.uk/biostudies/studies/S-EPMC5828012biostudies-literatureUnknown358(6368)The spliceosome undergoes dramatic changes in a splicing cycle. Structures of B, B^act, C, C*, and intron lariat spliceosome complexes revealed mechanisms of 5'-splice site (ss) recognition, branching, and intron release, but lacked information on 3'-ss recognition, exon ligation, and exon release. Here we report a cryo-electron microscopy structure of the postcatalytic P complex at 3.3-angstrom resolution, revealing that the 3' ss is mainly recognized through non-Watson-Crick base pairing with the 5' ss and branch point. Furthermore, one or more unidentified proteins become stably associated with the P complex, securing the 3' exon and potentially regulating activity of the helicase Prp22. Prp22 binds nucleotides 15 to 21 in the 3' exon, enabling it to pull the intron-exon or ligated exons in a 3' to 5' direction to achieve 3'-ss proofreading or exon release, respectively.Science (New York, N.Y.)Structure of the yeast spliceosomal postcatalytic P complex.PMC5828012award358773R01 GM114178R01 GM071940award358772U24 GM116792S10 OD018111R01 AI094386AI094386P41 GM103311GM071940award360448GM114178Zhou ZHLi XJiang JHill RCZhao RCui YLiu SZhang LHansen KC39falseStructure of the yeast spliceosomal postcatalytic P complex.The spliceosome undergoes dramatic changes in a splicing cycle. Structures of B, B^act, C, C*, and intron lariat spliceosome complexes revealed mechanisms of 5'-splice site (ss) recognition, branching, and intron release, but lacked information on 3'-ss recognition, exon ligation, and exon release. Here we report a cryo-electron microscopy structure of the postcatalytic P complex at 3.3-angstrom resolution, revealing that the 3' ss is mainly recognized through non-Watson-Crick base pairing with the 5' ss and branch point. Furthermore, one or more unidentified proteins become stably associated with the P complex, securing the 3' exon and potentially regulating activity of the helicase Prp22. Prp22 binds nucleotides 15 to 21 in the 3' exon, enabling it to pull the intron-exon or ligated exons in a 3' to 5' direction to achieve 3'-ss proofreading or exon release, respectively.2017-01-01T00:00:00Z2017 Dec2024-11-07T03:40:08.555Z2019-03-26T23:04:27ZS-EPMC58280122914687010.1126/science.aar3462