Open Access
PLoS Genetics, volume 11, issue 2, pages e1004999
The Exosome Component Rrp6 Is Required for RNA Polymerase II Termination at Specific Targets of the Nrd1-Nab3 Pathway
1
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America
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2
Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, United States of America,
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3
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America,
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Publication type: Journal Article
Publication date: 2015-02-13
Journal:
PLoS Genetics
Quartile SCImago
Q1
Quartile WOS
Q1
Impact factor: 4.5
ISSN: 15537390, 15537404
PubMed ID:
25680078
Cancer Research
Molecular Biology
Genetics
Ecology, Evolution, Behavior and Systematics
Genetics (clinical)
Abstract
The exosome and its nuclear specific subunit Rrp6 form a 3’-5’ exonuclease complex that regulates diverse aspects of RNA biology including 3’ end processing and degradation of a variety of noncoding RNAs (ncRNAs) and unstable transcripts. Known targets of the nuclear exosome include short (<1000 bp) RNAPII transcripts such as small noncoding RNAs (snRNAs), cryptic unstable transcripts (CUTs), and some stable unannotated transcripts (SUTs) that are terminated by an Nrd1, Nab3, and Sen1 (NNS) dependent mechanism. NNS-dependent termination is coupled to RNA 3’ end processing and/or degradation by the Rrp6/exosome in yeast. Recent work suggests Nrd1 is necessary for transcriptome surveillance, regulating promoter directionality and suppressing antisense transcription independently of, or prior to, Rrp6 activity. It remains unclear whether Rrp6 is directly involved in termination; however, Rrp6 has been implicated in the 3’ end processing and degradation of ncRNA transcripts including CUTs. To determine the role of Rrp6 in NNS termination globally, we performed RNA sequencing (RNA-Seq) on total RNA and perform ChIP-exo analysis of RNA Polymerase II (RNAPII) localization. Deletion of RRP6 promotes hyper-elongation of multiple NNS-dependent transcripts resulting from both improperly processed 3’ RNA ends and faulty transcript termination at specific target genes. The defects in RNAPII termination cause transcriptome-wide changes in mRNA expression through transcription interference and/or antisense repression, similar to previously reported effects of depleting Nrd1 from the nucleus. Elongated transcripts were identified within all classes of known NNS targets with the largest changes in transcription termination occurring at CUTs. Interestingly, the extended transcripts that we have detected in our studies show remarkable similarity to Nrd1-unterminated transcripts at many locations, suggesting that Rrp6 acts with the NNS complex globally to promote transcription termination in addition to 3’ end RNA processing and/or degradation at specific targets.
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- We do not take into account publications that without a DOI.
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- Statistics recalculated weekly.
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Fox M. J. et al. The Exosome Component Rrp6 Is Required for RNA Polymerase II Termination at Specific Targets of the Nrd1-Nab3 Pathway // PLoS Genetics. 2015. Vol. 11. No. 2. p. e1004999.
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Fox M. J., Gao H., Smith Kinnaman W. R., Liu Y., Mosley A. L. The Exosome Component Rrp6 Is Required for RNA Polymerase II Termination at Specific Targets of the Nrd1-Nab3 Pathway // PLoS Genetics. 2015. Vol. 11. No. 2. p. e1004999.
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TY - JOUR
DO - 10.1371/journal.pgen.1004999
UR - https://doi.org/10.1371%2Fjournal.pgen.1004999
TI - The Exosome Component Rrp6 Is Required for RNA Polymerase II Termination at Specific Targets of the Nrd1-Nab3 Pathway
T2 - PLoS Genetics
AU - Fox, Melanie J
AU - Gao, Hongyu
AU - Smith Kinnaman, Whitney R
AU - Liu, Yunlong
AU - Mosley, Amber L.
PY - 2015
DA - 2015/02/13 00:00:00
PB - Public Library of Science (PLoS)
SP - e1004999
IS - 2
VL - 11
PMID - 25680078
SN - 1553-7390
SN - 1553-7404
ER -
Cite this
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@article{2015_Fox,
author = {Melanie J Fox and Hongyu Gao and Whitney R Smith Kinnaman and Yunlong Liu and Amber L. Mosley},
title = {The Exosome Component Rrp6 Is Required for RNA Polymerase II Termination at Specific Targets of the Nrd1-Nab3 Pathway},
journal = {PLoS Genetics},
year = {2015},
volume = {11},
publisher = {Public Library of Science (PLoS)},
month = {feb},
url = {https://doi.org/10.1371%2Fjournal.pgen.1004999},
number = {2},
pages = {e1004999},
doi = {10.1371/journal.pgen.1004999}
}
Cite this
MLA
Copy
Fox, Melanie J., et al. “The Exosome Component Rrp6 Is Required for RNA Polymerase II Termination at Specific Targets of the Nrd1-Nab3 Pathway.” PLoS Genetics, vol. 11, no. 2, Feb. 2015, p. e1004999. https://doi.org/10.1371%2Fjournal.pgen.1004999.