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8ro0

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Structure of the C. elegans Intron Lariat Spliceosome primed for disassembly (ILS')

Structural highlights

8ro0 is a 10 chain structure with sequence from Caenorhabditis elegans. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 2.9Å
Ligands:	, , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PRP8_CAEEL Functions as a scaffold that mediates the ordered assembly of spliceosomal proteins and snRNAs. Required for the assembly of the U4/U6-U5 tri-snRNP complex. Functions as scaffold that positions spliceosomal U2, U5 and U6 snRNAs at splice sites on pre-mRNA substrates, so that splicing can occur. Interacts with both the 5' and the 3' splice site (By similarity).

Publication Abstract from PubMed

Pre-mRNA splicing requires the assembly, remodeling, and disassembly of the multi-megadalton ribonucleoprotein complex called the spliceosome(1). Recent studies have shed light on spliceosome assembly and remodeling for catalysis(2-6), but the mechanism of disassembly remains unclear. Here, we report 2.6 to 3.2 A resolution cryo-electron microscopy structures of nematode and human terminal intron-lariat spliceosomes along with biochemical and genetic data. Our results uncover how four disassembly factors and the conserved RNA helicase DHX15 initiate spliceosome disassembly. The disassembly factors probe large inner and outer spliceosome surfaces to detect the release of ligated mRNA. Two of these factors, TFIP11 and C19L1, and three general spliceosome subunits, SYF1, SYF2 and SDE2, then dock and activate DHX15 on the catalytic U6 snRNA to initiate disassembly. U6 thus controls both the start(5) and end of pre-mRNA splicing. Taken together, our results explain the molecular basis of canonical spliceosome disassembly and provide a framework to understand general spliceosomal RNA helicase control and the discard of aberrant spliceosomes.

Mechanism for the initiation of spliceosome disassembly.,Vorlander MK, Rothe P, Kleifeld J, Cormack E, Veleti L, Riabov-Bassat D, Fin L, Phillips AW, Cochella L, Plaschka C Nature. 2024 Jun 26. doi: 10.1038/s41586-024-07741-1. PMID:38925148^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Vorländer MK, Rothe P, Kleifeld J, Cormack E, Veleti L, Riabov-Bassat D, Fin L, Phillips AW, Cochella L, Plaschka C. Mechanism for the initiation of spliceosome disassembly. Nature. 2024 Jun 26. PMID:38925148 doi:10.1038/s41586-024-07741-1