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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.

Authors

Ashley P.E. Roberts

Rachel Doidge



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 http://eprints.nottingham.ac.uk/id/eprint/3109
Publisher URL http://nar.oxfordjournals.org/content/42/2/1257
Copyright Statement Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0

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