ZFIN ID: ZDB-PUB-190302-2
Selective Roles of Vertebrate PCF11 in Premature and Full-Length Transcript Termination
Kamieniarz-Gdula, K., Gdula, M.R., Panser, K., Nojima, T., Monks, J., Wiśniewski, J.R., Riepsaame, J., Brockdorff, N., Pauli, A., Proudfoot, N.J.
Date: 2019
Source: Molecular Cell   74(1): 158-172.e9 (Journal)
Registered Authors: Panser, Karin, Pauli, Andrea
Keywords: PCF11, RNA 3′ processing, alternative polyadenylation, attenuation, autoregulation, human, premature termination, regulation of gene expression, transcription termination, zebrafish
Microarrays: GEO:GSE123105, GEO:GSE124555
MeSH Terms:
  • Animals
  • Animals, Genetically Modified
  • Binding Sites
  • Gene Expression Regulation, Developmental
  • HeLa Cells
  • Humans
  • Mutation
  • Polyadenylation
  • Protein Binding
  • RNA Cleavage
  • RNA Polymerase II/genetics
  • RNA Polymerase II/metabolism
  • RNA, Messenger/biosynthesis*
  • RNA, Messenger/genetics
  • Transcription Termination, Genetic*
  • Zebrafish/genetics
  • Zebrafish/metabolism*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
  • mRNA Cleavage and Polyadenylation Factors/genetics
  • mRNA Cleavage and Polyadenylation Factors/metabolism*
PubMed: 30819644 Full text @ Mol. Cell
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ABSTRACT
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 consequent gene downregulation. 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.
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