title: CryoEM structures of two spliceosomal complexes: starter and dessert at the spliceosome feast.
abstract: The spliceosome is formed on pre-mRNA substrates from five small nuclear ribonucleoprotein particles (U1, U2, U4/U6 and U5 snRNPs), and numerous non-snRNP factors. Saccharomyces cerevisiae U4/U6.U5 tri-snRNP comprises U5 snRNA, U4/U6 snRNA duplex and approximately 30 proteins and represents a substantial part of the spliceosome before activation. Schizosaccharomyces pombe U2.U6.U5 spliceosomal complex is a post-catalytic intron lariat spliceosome containing U2 and U5 snRNPs, NTC (nineteen complex), NTC-related proteins (NTR), U6 snRNA, and an RNA intron lariat. Two recent papers describe near-complete atomic structures of these complexes based on cryoEM single-particle analysis. The U4/U6.U5 tri-snRNP structure provides crucial insight into the activation mechanism of the spliceosome. The U2.U6.U5 complex reveals the striking architecture of NTC and NTR and important features of the group II intron-like catalytic RNA core remaining after spliced mRNA is released. These two structures greatly advance our understanding of the mechanism of pre-mRNA splicing.
authors.affiliation: MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH UK.
authors.forename: Thi Hoang Duong
authors.initials: TH
authors.lastname: Nguyen
authors.affiliation: MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH UK.
authors.forename: Wojciech P
authors.initials: WP
authors.lastname: Galej
authors.affiliation: MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH UK.
authors.forename: Sebastian M
authors.initials: SM
authors.lastname: Fica
authors.affiliation: MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH UK.
authors.forename: Pei-Chun
authors.initials: PC
authors.lastname: Lin
authors.affiliation: MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH UK. Electronic address: newman@mrc-lmb.cam.ac.uk.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Newman
authors.affiliation: MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH UK. Electronic address: kn@mrc-lmb.cam.ac.uk.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Nagai
mesh_terms: D000818:Animals; D020285:Cryoelectron Microscopy; D006801:Humans; D046911:Macromolecular Substances / Q000737:chemistry* / Q000648:ultrastructure*; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D011487:Protein Conformation; D012342:RNA, Small Nuclear / Q000737:chemistry / Q000378:metabolism; D017411:Ribonucleoproteins, Small Nuclear / Q000737:chemistry / Q000378:metabolism; D012568:Schizosaccharomyces / Q000378:metabolism; D017381:Spliceosomes / Q000737:chemistry* / Q000648:ultrastructure*
chemical_list: D046911:Macromolecular Substances; D012342:RNA, Small Nuclear; D017411:Ribonucleoproteins, Small Nuclear; C405482:U4 small nuclear RNA; C405485:U5 small nuclear RNA; C405486:U6 small nuclear RNA