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

Molecular Cell
Kinga Kamieniarz-GdulaN J Proudfoot

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.

Associated Datasets

Citations

Sep 19, 2019·Genes & Development·Deirdre C TatomerJeremy E Wilusz
Jun 4, 2019·Journal of Molecular Cell Biology·Michaela Müller-McNicollJan Medenbach
Sep 27, 2019·Nature Reviews. Drug Discovery·Joana DesterroMaria Carmo-Fonseca
Mar 19, 2020·PLoS Genetics·Jose F VictorinoAmber L Mosley
May 14, 2020·Transcription·Danielle E LyonsMelanie Ott
Feb 23, 2020·Cold Spring Harbor Symposia on Quantitative Biology·Deirdre C Tatomer, Jeremy E Wilusz
Jul 31, 2020·Transcription·Michael Tellier, Shona Murphy
Mar 5, 2020·Wiley Interdisciplinary Reviews. RNA·Michael TellierShona Murphy
Sep 26, 2020·Nucleic Acids Research·Federico MariniSven Danckwardt
Sep 29, 2020·Nucleic Acids Research·Jackson B TrotmanJ Mauro Calabrese
Jul 28, 2020·Nucleic Acids Research·Mengjun WuAlbin Sandelin
Jan 2, 2021·Molecular Cell·Søren Lykke-AndersenTorben Heick Jensen
Oct 25, 2019·Genes & Diseases·Fuwen YuanQianben Wang
Nov 20, 2020·Nature Reviews. Molecular Cell Biology·Melvin Noe GonzalezJesper Q Svejstrup
Mar 25, 2021·Cell Reports·Nesrine BenkafadarStefan Heller
Apr 30, 2021·ELife·Chris EstellSteven West
Jul 11, 2021·Nucleic Acids Research·Jihae ShinBin Tian
Sep 23, 2021·Proceedings of the National Academy of Sciences of the United States of America·Caitlin E MonaghanSusan L Ackerman

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Datasets Mentioned

BETA
GSE62001
GSE32900
GSE111882
GSE97827
GSE60358
GSE123105

Methods Mentioned

BETA
immunoprecipitation
chrRNA-seq
ChIP-seq
ChIP
electrophoresis
transfection
FACS
PCR
scraping
RNA-seq

Software Mentioned

QuantSeq
Bowtie2
STAR2
Fiji
Epicenter
UCSC genome browser
STAR
Bigwig
R Bioconductor
MACS2

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