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Virology. 2017 Jul;507:231-241. doi: 10.1016/j.virol.2017.04.014. Epub 2017 Apr 26.

Cellular DEAD-box RNA helicase DDX6 modulates interaction of miR-122 with the 5' untranslated region of hepatitis C virus RNA.

Author information

1
Department of Biological Sciences, The RNA Institute, University at Albany-SUNY, Albany, NY 12222, USA.
2
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
3
Department of Biological Sciences, The RNA Institute, University at Albany-SUNY, Albany, NY 12222, USA. Electronic address: ctpager@albany.edu.

Abstract

Hepatitis C virus (HCV) subverts the cellular DEAD-box RNA helicase DDX6 to promote virus infection. Using polysome gradient analysis and the subgenomic HCV Renilla reporter replicon genome, we determined that DDX6 does not affect HCV translation. Rather expression of the subgenomic HCV Renilla luciferase reporter at late times, as well as labeling of newly synthesized viral RNA with 4-thiouridine showed that DDX6 modulates replication. Because DDX6 is an effector protein of the microRNA pathway, we also investigated its role in miR-122-directed HCV gene expression. Similar to sequestering miR-122, depletion of DDX6 modulated HCV RNA stability. Interestingly, miR-122-HCV RNA interaction assays with mutant HCV genomes sites and compensatory exogenous miR-122 showed that DDX6 affects the function of miR-122 at one particular binding site. We propose that DDX6 facilitates the miR-122 interaction with HCV 5' UTR, which is necessary for stabilizing the viral genome and the switch between translation and replication.

KEYWORDS:

DDX6; DEAD-box RNA helicase; Hepatitis C virus; RNA stability; Replication; miR-122

PMID:
28456022
PMCID:
PMC5549679
DOI:
10.1016/j.virol.2017.04.014
[Indexed for MEDLINE]
Free PMC Article

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