West Nile virus encodes a microRNA-like small RNA in the 3' untranslated region which up-regulates GATA4 mRNA and facilitates virus replication in mosquito cells

Hussain, Mazhar, Torres, Shessy, Schnettler, Esther, Funk, Anneke, Grundhoff, Adam, Pijlman, Gorben P., Khromykh, Alexander A. and Asgari, Sassan (2012) West Nile virus encodes a microRNA-like small RNA in the 3' untranslated region which up-regulates GATA4 mRNA and facilitates virus replication in mosquito cells. Nucleic Acids Research, 40 5: 2210-2223. doi:10.1093/nar/gkr848


Author Hussain, Mazhar
Torres, Shessy
Schnettler, Esther
Funk, Anneke
Grundhoff, Adam
Pijlman, Gorben P.
Khromykh, Alexander A.
Asgari, Sassan
Title West Nile virus encodes a microRNA-like small RNA in the 3' untranslated region which up-regulates GATA4 mRNA and facilitates virus replication in mosquito cells
Formatted title
West Nile virus encodes a microRNA-like small RNA in the 3′ untranslated region which up-regulates GATA4 mRNA and facilitates virus replication in mosquito cells
Journal name Nucleic Acids Research   Check publisher's open access policy
ISSN 0305-1048
1362-4962
Publication date 2012-03
Year available 2011
Sub-type Article (original research)
DOI 10.1093/nar/gkr848
Open Access Status DOI
Volume 40
Issue 5
Start page 2210
End page 2223
Total pages 14
Place of publication Oxford, United Kingdom
Publisher Oxford University Press
Collection year 2012
Language eng
Formatted abstract
West Nile virus (WNV) belongs to a group of medically important single-stranded, positive-sense RNA viruses causing deadly disease outbreaks around the world. The 3′ untranslated region (3′-UTR) of the flavivirus genome, in particular the terminal 3′ stem–loop (3′SL) fulfils multiple functions in virus replication and virus–host interactions. Using the Kunjin strain of WNV (WNVKUN), we detected a virally encoded small RNA, named KUN-miR-1, derived from 3′SL. Transcription of WNVKUN pre-miRNA (3′SL) in mosquito cells either from plasmid or Semliki Forest virus (SFV) RNA replicon resulted in the production of mature KUN-miR-1. Silencing of Dicer-1 but not Dicer-2 led to a reduction in the miRNA levels. Further, when a synthetic inhibitor of KUN-miR-1 was transfected into mosquito cells, replication of viral RNA was significantly reduced. Using cloning and bioinformatics approaches, we identified the cellular GATA4 mRNA as a target for KUN-miR-1. KUN-miR-1 produced in mosquito cells during virus infection or from plasmid DNA, SFV RNA replicon or mature miRNA duplex increased accumulation of GATA4 mRNA. Depletion of GATA4 mRNA by RNA silencing led to a significant reduction in virus RNA replication while a KUN-miR-1 RNA mimic enhanced replication of a mutant WNVKUN virus producing reduced amounts of KUN-miR-1, suggesting that GATA4-induction via KUN-miR-1 plays an important role in virus replication.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published ahead of print: November 12, 2011

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2012 Collection
School of Biological Sciences Publications
School of Chemistry and Molecular Biosciences
 
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Created: Tue, 18 Oct 2011, 13:25:03 EST by Prof Sassan Asgari on behalf of School of Biological Sciences