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

Moon, Stephanie L., Anderson, John R., Kumagai, Yutaro, Wilusz, Carol J., Akira, Shizuo, Khromykh, Alexander A. and Wilusz, Jeffrey (2012) A noncoding RNA produced by arthropod-borne flaviviruses inhibits the cellular exoribonuclease XRN1 and alters host mRNA stability. RNA, 18 11: 2029-2040.


Author Moon, Stephanie L.
Anderson, John R.
Kumagai, Yutaro
Wilusz, Carol J.
Akira, Shizuo
Khromykh, Alexander A.
Wilusz, Jeffrey
Title A noncoding RNA produced by arthropod-borne flaviviruses inhibits the cellular exoribonuclease XRN1 and alters host mRNA stability
Journal name RNA   Check publisher's open access policy
ISSN 1355-8382
1469-9001
Publication date 2012-11-18
Sub-type Article (original research)
DOI 10.1261/rna.034330.112
Volume 18
Issue 11
Start page 2029
End page 2040
Total pages 12
Place of publication Woodbury, NY, United States
Publisher Cold Spring Harbor Laboratory Press
Collection year 2013
Language eng
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.
Keyword Flavivirus
mRNA decay
mRNA stability
Noncoding RNA
Virus-host interaction
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published online: 24 September 2012.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
School of Chemistry and Molecular Biosciences
 
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Created: Fri, 23 Nov 2012, 10:47:50 EST by Mrs Louise Nimwegen on behalf of School of Chemistry & Molecular Biosciences