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PMID: 23006624 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

A noncoding RNA produced by arthropod-borne flaviviruses inhibits the cellular exoribonuclease XRN1 and alters host mRNA stability.

RNA (New York, N.Y.) ·Vol. 18 ·No. 11 ·2012-11-00 ·Pages 2029-40

Moon SL, Anderson JR, Kumagai Y, Wilusz CJ, Akira S, Khromykh AA, Wilusz J

Abstract

All arthropod-borne flaviviruses generate a short noncoding RNA (sfRNA) from the viral 3' untranslated region during infection due to stalling of the cellular 5'-to-3' exonuclease XRN1. We show here that formation of sfRNA also inhibits XRN1 activity. Cells infected with Dengue or Kunjin viruses accumulate uncapped mRNAs, decay intermediates normally targeted by XRN1. XRN1 repression also resulted in the increased overall stability of cellular mRNAs in flavivirus-infected cells. Importantly, a mutant Kunjin virus that cannot form sfRNA but replicates to normal levels failed to affect host mRNA stability or XRN1 activity. Expression of sfRNA in the absence of viral infection demonstrated that sfRNA formation was directly responsible for the stabilization of cellular mRNAs. Finally, numerous cellular mRNAs were differentially expressed in an sfRNA-dependent fashion in a Kunjin virus infection. We conclude that flaviviruses incapacitate XRN1 during infection and dysregulate host mRNA stability as a result of sfRNA formation.

MeSH Terms
3' Untranslated Regions Aedes/cytology,virology Animals Cell Line Cricetinae Dengue Virus/genetics,physiology Exoribonucleases/antagonists & inhibitors,chemistry,metabolism Gene Expression Regulation Half-Life Host-Pathogen Interactions Humans Insect Proteins/antagonists & inhibitors,chemistry,metabolism Microtubule-Associated Proteins/antagonists & inhibitors,chemistry,metabolism Oligonucleotide Array Sequence Analysis RNA Stability RNA, Messenger/chemistry,metabolism RNA, Untranslated/chemistry,metabolism,physiology RNA, Viral/chemistry,metabolism,physiology Saccharomyces cerevisiae Proteins/antagonists & inhibitors,chemistry Transcriptome West Nile virus/genetics,physiology
Chemicals
3' Untranslated Regions Insect Proteins Microtubule-Associated Proteins RNA, Messenger RNA, Untranslated RNA, Viral Saccharomyces cerevisiae Proteins Exoribonucleases XRN1 protein, S cerevisiae XRN1 protein, human
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Moon Stephanie L
Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado 80523, USA.
Anderson John R
Kumagai Yutaro
Wilusz Carol J
Akira Shizuo
Khromykh Alexander A
Wilusz Jeffrey
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Article Info
Journal
RNA (New York, N.Y.)
Abbr.
RNA
ISSN
1469-9001
DOI
10.1261/rna.034330.112
Published
2012-11-00
Epub
2012-00-24
Pages
2029-40
Language
English
Region
United States
NLM ID
9509184
PMCID
PMC3479393
Subset
IM
Grants
NIAID NIH HHS · R01 AI063434 · United States
NIAID NIH HHS · U54 AI065357 · United States
NIAID NIH HHS · AI063434 · United States
NIAID NIH HHS · U54 AI-065357 · United States
External Links
PubMed source DOI: 10.1261/rna.034330.112 PMC Full Text View journal details
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