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-Structure paper
Title | A direct interaction between CPF and RNA Pol II links RNA 3' end processing to transcription. |
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Journal, issue, pages | Mol Cell, Vol. 83, Issue 24, Page 4461-4478.e13, Year 2023 |
Publish date | Dec 21, 2023 |
Authors | Manuel Carminati / Juan B Rodríguez-Molina / M Cemre Manav / Dom Bellini / Lori A Passmore / |
PubMed Abstract | Transcription termination by RNA polymerase II (RNA Pol II) is linked to RNA 3' end processing by the cleavage and polyadenylation factor (CPF or CPSF). CPF contains endonuclease, poly(A) polymerase, ...Transcription termination by RNA polymerase II (RNA Pol II) is linked to RNA 3' end processing by the cleavage and polyadenylation factor (CPF or CPSF). CPF contains endonuclease, poly(A) polymerase, and protein phosphatase activities, which cleave and polyadenylate pre-mRNAs and dephosphorylate RNA Pol II to control transcription. Exactly how the RNA 3' end processing machinery is coupled to transcription remains unclear. Here, we combine in vitro reconstitution, structural studies, and genome-wide analyses to show that yeast CPF physically and functionally interacts with RNA Pol II. Surprisingly, CPF-mediated dephosphorylation promotes the formation of an RNA Pol II stalk-to-stalk homodimer in vitro. This dimer is compatible with transcription but not with the binding of transcription elongation factors. Disruption of the dimerization interface in cells causes transcription defects, including altered RNA Pol II abundance on protein-coding genes, tRNA genes, and intergenic regions. We hypothesize that RNA Pol II dimerization may provide a mechanistic basis for the allosteric model of transcription termination. |
External links | Mol Cell / PubMed:38029752 / PubMed Central |
Methods | EM (single particle) / X-ray diffraction |
Resolution | 1.85 - 4.6 Å |
Structure data | EMDB-15358: Structure of dimeric yeast RNA polymerase II bound to a transcription bubble (consensus map) EMDB-15359: Structure of dimeric yeast RNA polymerase II bound to a transcription bubble (focused map of monomer 1) EMDB-15360: Structure of dimeric yeast RNA polymerase II bound to a transcription bubble (focused map of monomer 2) PDB-8a8f: |
Chemicals | ChemComp-MN: ChemComp-PO4: ChemComp-HOH: |
Source |
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Keywords | GENE REGULATION / Ser/Thr phosphatase / regulatory subunit / RNA / transcription termination |