PUBLICATION

Selective Roles of Vertebrate PCF11 in Premature and Full-Length Transcript Termination

Authors
Kamieniarz-Gdula, K., Gdula, M.R., Panser, K., Nojima, T., Monks, J., Wiśniewski, J.R., Riepsaame, J., Brockdorff, N., Pauli, A., Proudfoot, N.J.
ID
ZDB-PUB-190302-2
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
Datasets
GEO:GSE124555, GEO:GSE123105
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
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.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping