The P body protein LSm1 contributes to stimulation of hepatitis C virus translation, but not replication, by microRNA-122

Roberts, Ashley P.E.; Doidge, Rachel; Tarr, Alexander W.; Jopling, Catherine L.

Abstract

The P body protein LSm1 stimulates translation and replication of hepatitis C virus (HCV). As the liver-specific microRNA-122 (miR-122) is required for HCV replication and is associated with P bodies, we investigated whether regulation of HCV by LSm1 involves miR-122. Here, we demonstrate that LSm1 contributes to activation of HCV internal ribosome entry site (IRES)-driven translation by miR-122. This role for LSm1 is specialized for miR-122 translation activation, as LSm1 depletion does not affect the repressive function of miR-122 at 3′ untranslated region (UTR) sites, or miR-122–mediated cleavage at a perfectly complementary site. We find that LSm1 does not influence recruitment of the microRNA (miRNA)-induced silencing complex to the HCV 5′UTR, implying that it regulates miR-122 function subsequent to target binding. In contrast to the interplay between miR-122 and LSm1 in translation, we find that LSm1 is not required for miR-122 to stimulate HCV replication, suggesting that miR-122 regulation of HCV translation and replication have different requirements. For the first time, we have identified a protein factor that specifically contributes to activation of HCV IRES-driven translation by miR-122, but not to other activities of the miRNA. Our results enhance understanding of the mechanisms by which miR-122 and LSm1 regulate HCV.

Citation

Roberts, A. P., Doidge, R., Tarr, A. W., & Jopling, C. L. (2014). The P body protein LSm1 contributes to stimulation of hepatitis C virus translation, but not replication, by microRNA-122. Nucleic Acids Research, 42(2), 1257-1269. https://doi.org/10.1093/nar/gkt941

• Journal Article Type: Article
• Acceptance Date: Sep 25, 2013
• Online Publication Date: Oct 18, 2013
• Publication Date: Jan 1, 2014
• Deposit Date: May 2, 2014
• Publicly Available Date: May 2, 2014
• Journal: Nucleic Acids Research
• Print ISSN: 0305-1048
• Electronic ISSN: 1362-4962
• Publisher: Oxford University Press
• Peer Reviewed: Peer Reviewed
• Volume: 42
• Issue: 2
• Pages: 1257-1269
• DOI: https://doi.org/10.1093/nar/gkt941
• Public URL: https://nottingham-repository.worktribe.com/output/997642
• Publisher URL: http://nar.oxfordjournals.org/content/42/2/1257