title: Requirements for human Dicer and TRBP in microRNA-122 regulation of HCV translation and RNA abundance.
abstract: MicroRNA-122 (miR-122) promotes Hepatitis C Virus (HCV) RNA stability, accumulation, and translation through hybridization with the 5' untranslated region (5' UTR) of the HCV genome. Depletion of Dicer and TRBP, proteins involved in miRNA biogenesis, reduced HCV RNA accumulation, mature duplex miR-122 abundance, and miR-122 directed mRNA translation suppression, suggesting roles in miR-122 processing. HCV RNA accumulation independent of endogenous mature duplex miR-122 was not affected by Dicer knockdown, suggesting that Dicer is required solely for miR-122 biogenesis, but TRBP knockdown reduced HCV RNA accumulation in this system, suggesting an additional role in supporting HCV RNA accumulation. Mature duplex miR-122 and pre-miR-122 hairpin, but not single-stranded miR-122 (guide or * strand), augmented HCV RNA accumulation and translation, and Dicer and TRBP were essential for the activity of pre-miR-122 in mouse fibroblasts. Thus, canonical miRNA processing and strand selection is essential for the activity of miR-122 on HCV translation and RNA accumulation.
authors.affiliation: Department of Microbiology and Immunology, University of Saskatchewan, Saskatoon, SK, Canada S7N 5E5.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.forename: Adam
authors.initials: A
authors.lastname: Huys
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Thibault
authors.forename: Joyce A
authors.initials: JA
authors.lastname: Wilson
mesh_terms: D020121:5' Untranslated Regions; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002478:Cells, Cultured; D053487:DEAD-box RNA Helicases / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D016679:Genome, Viral; D016174:Hepacivirus / Q000235:genetics* / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D008954:Models, Biological; D014176:Protein Biosynthesis; D012323:RNA Processing, Post-Transcriptional; D020871:RNA Stability; D034741:RNA, Small Interfering / Q000235:genetics; D012367:RNA, Viral / Q000235:genetics* / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D043244:Ribonuclease III / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication; D000099253:Trans-Activation Responsive RNA-Binding Protein
chemical_list: D020121:5' Untranslated Regions; D053487:DEAD-box RNA Helicases; D035683:MicroRNAs; D034741:RNA, Small Interfering; D012367:RNA, Viral; D016601:RNA-Binding Proteins; D043244:Ribonuclease III; D000099253:Trans-Activation Responsive RNA-Binding Protein; C531907:MIRN122 microRNA, human; C544354:Mirn122 microRNA, mouse; C408087:DICER1 protein, human; C509781:Dicer1 protein, mouse