8RO0

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

This is a non-PDB format compatible entry.

Summary for 8RO0

• Entry DOI: 10.2210/pdb8ro0/pdb
• Related: 8RO1 8RO2 9FMD
• EMDB information: 19397
• Descriptor: U2 snRNA, TPR_REGION domain-containing protein, Pre-mRNA-splicing factor SPF27, ... (40 entities in total)
• Functional Keywords: mrna, splicing, intorn lariat spliceosome, ils, pre-mrna
• Biological source: Caenorhabditis elegans; More
• Total number of polymer chains: 46
• Total formula weight: 2302471.70

Authors

Vorlaender, M.K.,Rothe, P.,Plaschka, C. (deposition date: 2024-01-11, release date: 2024-08-07, Last modification date: 2024-11-20)

Primary citation

Vorlander, M.K.,Rothe, P.,Kleifeld, J.,Cormack, E.D.,Veleti, L.,Riabov-Bassat, D.,Fin, L.,Phillips, A.W.,Cochella, L.,Plaschka, C.
Mechanism for the initiation of spliceosome disassembly.
Nature, 632:443-450, 2024

PubMed Abstract: Pre-mRNA splicing requires the assembly, remodeling, and disassembly of the multi-megadalton ribonucleoprotein complex called the spliceosome. Recent studies have shed light on spliceosome assembly and remodeling for catalysis, but the mechanism of disassembly remains unclear. Here, we report 2.6 to 3.2 Å 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 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.

PubMed: 38925148
DOI: 10.1038/s41586-024-07741-1

Experimental method

ELECTRON MICROSCOPY (2.9 Å)