6QDV

Human post-catalytic P complex spliceosome

This is a non-PDB format compatible entry.

Summary for 6QDV

• Entry DOI: 10.2210/pdb6qdv/pdb
• EMDB information: 4525
• Descriptor: U2 snRNA, PRKR-interacting protein 1, Ligated exons: MINX mRNA, ... (50 entities in total)
• Functional Keywords: spliceosome, rna, complex, splicing
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 54
• Total formula weight: 2322143.20

Authors

Fica, S.M.,Oubridge, C.,Wilkinson, M.E.,Newman, A.J.,Nagai, K. (deposition date: 2019-01-03, release date: 2019-02-20, Last modification date: 2024-11-13)

Primary citation

Fica, S.M.,Oubridge, C.,Wilkinson, M.E.,Newman, A.J.,Nagai, K.
A human postcatalytic spliceosome structure reveals essential roles of metazoan factors for exon ligation.
Science, 363:710-714, 2019

PubMed Abstract: During exon ligation, the spliceosome recognizes the 3'-splice site (3'SS) of precursor messenger RNA (pre-mRNA) through non-Watson-Crick pairing with the 5'SS and the branch adenosine, in a conformation stabilized by Prp18 and Prp8. Here we present the 3.3-angstrom cryo-electron microscopy structure of a human postcatalytic spliceosome just after exon ligation. The 3'SS docks at the active site through conserved RNA interactions in the absence of Prp18. Unexpectedly, the metazoan-specific FAM32A directly bridges the 5'-exon and intron 3'SS of pre-mRNA and promotes exon ligation, as shown by functional assays. CACTIN, SDE2, and NKAP-factors implicated in alternative splicing-further stabilize the catalytic conformation of the spliceosome during exon ligation. Together these four proteins act as exon ligation factors. Our study reveals how the human spliceosome has co-opted additional proteins to modulate a conserved RNA-based mechanism for 3'SS selection and to potentially fine-tune alternative splicing at the exon ligation stage.

PubMed: 30705154
DOI: 10.1126/science.aaw5569

Experimental method

ELECTRON MICROSCOPY (3.3 Å)