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-Structure paper
Title | Molecular basis for the activation of human spliceosome. |
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Journal, issue, pages | Nat Commun, Vol. 15, Issue 1, Page 6348, Year 2024 |
Publish date | Jul 27, 2024 |
![]() | Xiechao Zhan / Yichen Lu / Yigong Shi / ![]() |
PubMed Abstract | 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 ...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. |
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Methods | EM (single particle) |
Resolution | 3.0 - 4.2 Å |
Structure data | EMDB-35105, PDB-8i0p: EMDB-35107, PDB-8i0r: EMDB-35108, PDB-8i0s: EMDB-35109, PDB-8i0t: EMDB-35110, PDB-8i0u: EMDB-35111, PDB-8i0v: EMDB-35113, PDB-8i0w: |
Chemicals | ![]() ChemComp-GTP: ![]() ChemComp-MG: ![]() ChemComp-ZN: ![]() ChemComp-IHP: |
Source |
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![]() | SPLICING / spliceosome / pre-Bact complex / RNA splicing / PRP2 / activation / Bact-I complex / Bact-II complex / branching / Bact complex / PRP16 |