7W59

The cryo-EM structure of human pre-C*-I complex

Summary for 7W59

• Entry DOI: 10.2210/pdb7w59/pdb
• EMDB information: 32317
• Descriptor: Pre-mRNA-processing-splicing factor 8, Pre-mRNA-splicing factor RBM22, Spliceosome-associated protein CWC15 homolog, ... (45 entities in total)
• Functional Keywords: spliceosome, c* complex, rna splicing, prp22, exon ligation, fam192a, splicing
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 50
• Total formula weight: 2672892.16

Authors

Zhan, X.,Lu, Y.,Shi, Y. (deposition date: 2021-11-29, release date: 2022-06-22, Last modification date: 2024-10-16)

Primary citation

Zhan, X.,Lu, Y.,Zhang, X.,Yan, C.,Shi, Y.
Mechanism of exon ligation by human spliceosome.
Mol.Cell, 82:2769-2778.e4, 2022

PubMed Abstract: Pre-mRNA splicing involves two sequential reactions: branching and exon ligation. The C complex after branching undergoes remodeling to become the C complex, which executes exon ligation. Here, we report cryo-EM structures of two intermediate human spliceosomal complexes, pre-C-I and pre-C-II, both at 3.6 Å. In both structures, the 3' splice site is already docked into the active site, the ensuing 3' exon sequences are anchored on PRP8, and the step II factor FAM192A contacts the duplex between U2 snRNA and the branch site. In the transition of pre-C-I to pre-C-II, the step II factors Cactin, FAM32A, PRKRIP1, and SLU7 are recruited. Notably, the RNA helicase PRP22 is positioned quite differently in the pre-C-I, pre-C-II, and C complexes, suggesting a role in 3' exon binding and proofreading. Together with information on human C and C complexes, our studies recapitulate a molecular choreography of the C-to-C transition, revealing mechanistic insights into exon ligation.

PubMed: 35705093
DOI: 10.1016/j.molcel.2022.05.021

Experimental method

ELECTRON MICROSCOPY (3.6 Å)