9FMD

Integrative model of the human post-catalytic spliceosome (P-complex)

This is a non-PDB format compatible entry.

Summary for 9FMD

• Entry DOI: 10.2210/pdb9fmd/pdb
• Related: 6QDV 8RO0 8RO1 8RO2
• EMDB information: 4525
• Descriptor: PRKR-interacting protein 1, RNA-binding protein 8A, Protein mago nashi homolog, ... (59 entities in total)
• Functional Keywords: p-complex, spliceosome, splicing
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 63
• Total formula weight: 3373395.95

Authors

Rothe, P.,Plaschka, C.,Vorlaender, M.K. (deposition date: 2024-06-05, release date: 2024-07-10, Last modification date: 2024-12-11)

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: Precursor-mRNA (pre-mRNA) splicing requires the assembly, remodelling and disassembly of the multi-megadalton ribonucleoprotein complex called the spliceosome. Recent studies have shed light on spliceosome assembly and remodelling for catalysis, but the mechanism of disassembly remains unclear. Here we report 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 therefore controls both the start and end of pre-mRNA splicing. Taken together, our results explain the molecular basis of the initiation 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 (3.3 Å)