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TitleA unified mechanism for intron and exon definition and back-splicing.
Journal, issue, pagesNature, Vol. 573, Issue 7774, Page 375-380, Year 2019
Publish dateSep 4, 2019
AuthorsXueni Li / Shiheng Liu / Lingdi Zhang / Aaron Issaian / Ryan C Hill / Sara Espinosa / Shasha Shi / Yanxiang Cui / Kalli Kappel / Rhiju Das / Kirk C Hansen / Z Hong Zhou / Rui Zhao /
PubMed AbstractThe molecular mechanisms of exon definition and back-splicing are fundamental unanswered questions in pre-mRNA splicing. Here we report cryo-electron microscopy structures of the yeast spliceosomal E ...The molecular mechanisms of exon definition and back-splicing are fundamental unanswered questions in pre-mRNA splicing. Here we report cryo-electron microscopy structures of the yeast spliceosomal E complex assembled on introns, providing a view of the earliest event in the splicing cycle that commits pre-mRNAs to splicing. The E complex architecture suggests that the same spliceosome can assemble across an exon, and that it either remodels to span an intron for canonical linear splicing (typically on short exons) or catalyses back-splicing to generate circular RNA (on long exons). The model is supported by our experiments, which show that an E complex assembled on the middle exon of yeast EFM5 or HMRA1 can be chased into circular RNA when the exon is sufficiently long. This simple model unifies intron definition, exon definition, and back-splicing through the same spliceosome in all eukaryotes and should inspire experiments in many other systems to understand the mechanism and regulation of these processes.
External linksNature / PubMed:31485080 / PubMed Central
MethodsEM (single particle)
Resolution3.2 - 3.6 Å
Structure data

EMDB-0360, PDB-6n7p:
S. cerevisiae spliceosomal E complex (UBC4)
Method: EM (single particle) / Resolution: 3.6 Å

EMDB-0361, PDB-6n7r:
Saccharomyces cerevisiae spliceosomal E complex (ACT1)
Method: EM (single particle) / Resolution: 3.2 Å

Chemicals

ChemComp-ZN:
ZINC ION / Zinc

Source
  • saccharomyces cerevisiae (baker's yeast)
  • Baker's yeast (baker's yeast)
  • saccharomyces cerevisiae (strain atcc 204508 / s288c) (yeast)
  • saccharomyces cerevisiae s288c (yeast)
KeywordsCryoelectron Microscopy / Exons / Introns / Models, Molecular / Protein Structure, Quaternary / RNA Splicing / Saccharomyces cerevisiae / Saccharomyces cerevisiae Proteins / Spliceosomes / RNA BINDING PROTEIN / pre-mRNA splicing / spliceosome / E complex

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