title: The P body protein LSm1 contributes to stimulation of hepatitis C virus translation, but not replication, by microRNA-122.
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.
authors.affiliation: School of Pharmacy, Centre for Biomolecular Sciences, University of Nottingham, University Park, Nottingham NG7 2RD, UK.
authors.forename: Ashley P E
authors.initials: AP
authors.lastname: Roberts
authors.forename: Rachel
authors.initials: R
authors.lastname: Doidge
authors.forename: Alexander W
authors.initials: AW
authors.lastname: Tarr
authors.forename: Catherine L
authors.initials: CL
authors.lastname: Jopling
mesh_terms: D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D002460:Cell Line; D016174:Hepacivirus / Q000235:genetics* / Q000502:physiology; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D014176:Protein Biosynthesis; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D016601:RNA-Binding Proteins / Q000502:physiology*; D034743:RNA-Induced Silencing Complex / Q000378:metabolism; D014779:Virus Replication
chemical_list: D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; C464824:LSM1 protein, human; C531907:MIRN122 microRNA, human; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; D016601:RNA-Binding Proteins; D034743:RNA-Induced Silencing Complex