About: Viral nucleases induce an mRNA degradation-transcription feedback loop in mammalian cells

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An Entity of Type : schema:ScholarlyArticle, within Data Space : covidontheweb.inria.fr associated with source document(s)

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type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
title	Viral nucleases induce an mRNA degradation-transcription feedback loop in mammalian cells
Creator	Glaunsinger, Britt Abernathy, Emma Alla, Ravi Gilbertson, Sarah
source	Elsevier; Medline; PMC
abstract	Gamma-herpesviruses encode a cytoplasmic mRNA-targeting endonuclease, SOX, that cleaves most cellular mRNAs. Cleaved fragments are subsequently degraded by the cellular 5′-3′ mRNA exonuclease Xrn1, thereby suppressing cellular gene expression and facilitating viral evasion of host defenses. We reveal that mammalian cells respond to this widespread cytoplasmic mRNA decay by altering RNA polymerase II (RNAPII) transcription in the nucleus. Measuring RNAPII recruitment to promoters and nascent mRNA synthesis revealed that the majority of affected genes are transcriptionally repressed in SOX-expressing cells. The transcriptional feedback does not occur in response to the initial viral endonuclease-induced cleavage, but instead to degradation of the cleaved fragments by cellular exonucleases. In particular, Xrn1 catalytic activity is required for transcriptional repression. Notably, viral mRNA transcription escapes decay-induced repression, and this escape requires Xrn1. Collectively, these results indicate that mRNA decay rates impact transcription, and that gamma-herpesviruses use this feedback mechanism to facilitate viral gene expression.
has issue date	2015-08-01(xsd:dateTime)
bibo:doi	10.1016/j.chom.2015.06.019
bibo:pmid	26211836
has license	hybrid-oa
sha1sum (hex)	de628dce1f0a6c46f7bee9c40f83405b1b3b4ac1
schema:url	https://doi.org/10.1016/j.chom.2015.06.019
resource representing a document's title	Viral nucleases induce an mRNA degradation-transcription feedback loop in mammalian cells
has PubMed Central identifier	PMC4538998
has PubMed identifier	26211836
schema:publication	Cell Host & Microbe
resource representing a document's body	covid:de628dce1f0a6c46f7bee9c40f83405b1b3b4ac1#body_text
is schema:about of	named entity 'VIRAL' named entity 'MAMMALIAN' named entity 'INDUCE' named entity 'CELLS' named entity 'TRANSCRIPTION' named entity 'INFORMATION' named entity 'FEEDBACK LOOP' named entity 'MRNA DEGRADATION' named entity 'NUCLEASES' named entity 'SUPPLEMENTAL' named entity 'Transcription' named entity 'Viral' named entity 'fixed and stained' named entity 'secondary antibody' named entity '3T3' named entity 'CTCF' named entity 'Xrn1' named entity 'NIH' named entity 'duplexes' named entity 'Xrn1' named entity 'ImageJ' named entity 'staining' named entity 'methanol' named entity 'antibody' named entity '1:200' named entity 'formaldehyde' named entity 'cytoplasmic' named entity 'Xrn1' named entity 'BSA' named entity 'transfected' named entity 'fluorescence' named entity 'mRNA' named entity 'Nucleases' named entity 'Mammalian Cells' named entity 'Feedback Loop' named entity 'Feedback Loop' named entity 'mRNA' named entity 'Cells' named entity 'Information' named entity 'Viral'
is part of of	Viral nucleases induce an mRNA degradation-transcription feedback loop in mammalian cells covid:de628dce1f0a6c46f7bee9c40f83405b1b3b4ac1#body_text Gamma-herpesviruses encode a cytoplasmic mRNA-targeting endonuclease, SOX, that cleaves most cellular mRNAs. Cleaved fragments are subsequently degraded by the cellular 5′-3′ mRNA exonuclease Xrn1, thereby suppressing cellular gene expression and facilitating viral evasion of host defenses. We reveal that mammalian cells respond to this widespread cytoplasmic mRNA decay by altering RNA polymerase II (RNAPII) transcription in the nucleus. Measuring RNAPII recruitment to promoters and nascent mRNA synthesis revealed that the majority of affected genes are transcriptionally repressed in SOX-expressing cells. The transcriptional feedback does not occur in response to the initial viral endonuclease-induced cleavage, but instead to degradation of the cleaved fragments by cellular exonucleases. In particular, Xrn1 catalytic activity is required for transcriptional repression. Notably, viral mRNA transcription escapes decay-induced repression, and this escape requires Xrn1. Collectively, these results indicate that mRNA decay rates impact transcription, and that gamma-herpesviruses use this feedback mechanism to facilitate viral gene expression.

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