8C6J

Human spliceosomal PM5 C* complex

This is a non-PDB format compatible entry.

Summary for 8C6J

• Entry DOI: 10.2210/pdb8c6j/pdb
• EMDB information: 16452
• Descriptor: U2 snRNA, 116 kDa U5 small nuclear ribonucleoprotein component, Peptidyl-prolyl cis-trans isomerase-like 3, ... (59 entities in total)
• Functional Keywords: spliceosome, nucleus, splicing
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 63
• Total formula weight: 3425219.88

Authors

Dybkov, O.,Kastner, B.,Luehrmann, R. (deposition date: 2023-01-12, release date: 2023-07-12, Last modification date: 2024-11-06)

Primary citation

Dybkov, O.,Preussner, M.,El Ayoubi, L.,Feng, V.Y.,Harnisch, C.,Merz, K.,Leupold, P.,Yudichev, P.,Agafonov, D.E.,Will, C.L.,Girard, C.,Dienemann, C.,Urlaub, H.,Kastner, B.,Heyd, F.,Luehrmann, R.
Regulation of 3' splice site selection after step 1 of splicing by spliceosomal C* proteins.
Sci Adv, 9:eadf1785-, 2023

PubMed Abstract: Alternative precursor messenger RNA splicing is instrumental in expanding the proteome of higher eukaryotes, and changes in 3' splice site (3'ss) usage contribute to human disease. We demonstrate by small interfering RNA-mediated knockdowns, followed by RNA sequencing, that many proteins first recruited to human C* spliceosomes, which catalyze step 2 of splicing, regulate alternative splicing, including the selection of alternatively spliced NAGNAG 3'ss. Cryo-electron microscopy and protein cross-linking reveal the molecular architecture of these proteins in C* spliceosomes, providing mechanistic and structural insights into how they influence 3'ss usage. They further elucidate the path of the 3' region of the intron, allowing a structure-based model for how the C* spliceosome potentially scans for the proximal 3'ss. By combining biochemical and structural approaches with genome-wide functional analyses, our studies reveal widespread regulation of alternative 3'ss usage after step 1 of splicing and the likely mechanisms whereby C* proteins influence NAGNAG 3'ss choices.

PubMed: 36867703
DOI: 10.1126/sciadv.adf1785

Experimental method

ELECTRON MICROSCOPY (2.8 Å)