Selective roles of vertebrate PCF11 in premature and full-length transcript termination
Selective roles of vertebrate PCF11 in premature and full-length transcript termination
SUMMARY The pervasive nature of RNA polymerase II (Pol II) transcription requires efficient termination. A key player in this process is the cleavage and polyadenylation (CPA) factor PCF11, which directly binds to the Pol II C-terminal domain and dismantles elongating Pol II from DNA in vitro. We demonstrate that PCF11-mediated termination is essential for vertebrate development. A range of genomic analyses, including: mNET-seq, 3’ mRNA-seq, chromatin RNA-seq and ChIP-seq, reveals that PCF11 enhances transcription termination and stimulates early polyadenylation genome-wide. PCF11 binds preferentially between closely spaced genes, where it prevents transcriptional interference and downstream gene silencing. Notably, PCF11 is sub-stoichiometric to the CPA complex. Low levels of PCF11 are maintained by an auto-regulatory mechanism involving premature termination of its own transcript, and are important for normal development. Both in human cell culture and during zebrafish development, PCF11 selectively attenuates the expression of other transcriptional regulators by premature CPA and termination.
Kamieniarz-Gdula Kinga、Panser Karin、Monks Joan、Riepsaame Joey、Pauli Andrea、Proudfoot Nick J.、Brockdorff Neil、Wisniewski Jacek R.、Nojima Takayuki、Gdula Michal R.
Sir William Dunn School of Pathology, University of OxfordResearch Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC)Sir William Dunn School of Pathology, University of OxfordSir William Dunn School of Pathology, University of OxfordResearch Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC)Sir William Dunn School of Pathology, University of OxfordDepartment of Biochemistry, University of OxfordBiochemical Proteomics Group, Department of Proteomics and Signal Transduction, Max-Planck Institute of BiochemistrySir William Dunn School of Pathology, University of OxfordDepartment of Biochemistry, University of Oxford
分子生物学遗传学
Kamieniarz-Gdula Kinga,Panser Karin,Monks Joan,Riepsaame Joey,Pauli Andrea,Proudfoot Nick J.,Brockdorff Neil,Wisniewski Jacek R.,Nojima Takayuki,Gdula Michal R..Selective roles of vertebrate PCF11 in premature and full-length transcript termination[EB/OL].(2025-03-28)[2025-08-02].https://www.biorxiv.org/content/10.1101/491514.点此复制
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