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TitleMolecular basis for the activation of human spliceosome.
Journal, issue, pagesNat Commun, Vol. 15, Issue 1, Page 6348, Year 2024
Publish dateJul 27, 2024
AuthorsXiechao Zhan / Yichen Lu / Yigong Shi /
PubMed AbstractThe spliceosome executes pre-mRNA splicing through four sequential stages: assembly, activation, catalysis, and disassembly. Activation of the spliceosome, namely remodeling of the pre-catalytic ...The spliceosome executes pre-mRNA splicing through four sequential stages: assembly, activation, catalysis, and disassembly. Activation of the spliceosome, namely remodeling of the pre-catalytic spliceosome (B complex) into the activated spliceosome (B complex) and the catalytically activated spliceosome (B complex), involves major flux of protein components and structural rearrangements. Relying on a splicing inhibitor, we have captured six intermediate states between the B and B complexes: pre-B, B-I, B-II, B-III, B-IV, and post-B. Their cryo-EM structures, together with an improved structure of the catalytic step I spliceosome (C complex), reveal how the catalytic center matures around the internal stem loop of U6 snRNA, how the branch site approaches 5'-splice site, how the RNA helicase PRP2 rearranges to bind pre-mRNA, and how U2 snRNP undergoes remarkable movement to facilitate activation. We identify a previously unrecognized key role of PRP2 in spliceosome activation. Our study recapitulates a molecular choreography of the human spliceosome during its catalytic activation.
External linksNat Commun / PubMed:39068178 / PubMed Central
MethodsEM (single particle)
Resolution3.0 - 4.2 Å
Structure data

EMDB-35105, PDB-8i0p:
The cryo-EM structure of human pre-Bact complex
Method: EM (single particle) / Resolution: 3.4 Å

EMDB-35107, PDB-8i0r:
The cryo-EM structure of human Bact-I complex
Method: EM (single particle) / Resolution: 3.0 Å

EMDB-35108, PDB-8i0s:
The cryo-EM structure of human Bact-II complex
Method: EM (single particle) / Resolution: 4.2 Å

EMDB-35109, PDB-8i0t:
The cryo-EM structure of human Bact-III complex
Method: EM (single particle) / Resolution: 3.0 Å

EMDB-35110, PDB-8i0u:
The cryo-EM structure of human Bact-IV complex
Method: EM (single particle) / Resolution: 3.3 Å

EMDB-35111, PDB-8i0v:
The cryo-EM structure of human post-Bact complex
Method: EM (single particle) / Resolution: 3.0 Å

EMDB-35113, PDB-8i0w:
The cryo-EM structure of human C complex
Method: EM (single particle) / Resolution: 3.4 Å

Chemicals

ChemComp-GTP:
GUANOSINE-5'-TRIPHOSPHATE / GTP, energy-carrying molecule*YM

ChemComp-MG:
Unknown entry

ChemComp-ZN:
Unknown entry

ChemComp-IHP:
INOSITOL HEXAKISPHOSPHATE

Source
  • homo sapiens (human)
  • unidentified adenovirus
KeywordsSPLICING / spliceosome / pre-Bact complex / RNA splicing / PRP2 / activation / Bact-I complex / Bact-II complex / branching / Bact complex / PRP16

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