title: Refractoriness of hepatitis C virus internal ribosome entry site to processing by Dicer in vivo.
abstract: BACKGROUND
  Hepatitis C virus (HCV) is a positive-strand RNA virus harboring a highly structured internal ribosome entry site (IRES) in the 5' nontranslated region of its genome. Important for initiating translation of viral RNAs into proteins, the HCV IRES is composed of RNA structures reminiscent of microRNA precursors that may be targeted by the host RNA silencing machinery.
  
  
  RESULTS
  We report that HCV IRES can be recognized and processed into small RNAs by the human ribonuclease Dicer in vitro. Furthermore, we identify domains II, III and VI of HCV IRES as potential substrates for Dicer in vitro. However, maintenance of the functional integrity of the HCV IRES in response to Dicer overexpression suggests that the structure of the HCV IRES abrogates its processing by Dicer in vivo.
  
  
  CONCLUSIONS
  Our results suggest that the HCV IRES may have evolved to adopt a structure or a cellular context that is refractory to Dicer processing, which may contribute to viral escape of the host RNA silencing machinery.
authors.affiliation: Centre de Recherche en Rhumatologie et Immunologie, CHUL Research Center/CHUQ, 2705 Blvd Laurier, Quebec, QC, G1V 4G2, Canada. dominique.ouellet@crchul.ulaval.ca
authors.forename: Dominique L
authors.initials: DL
authors.lastname: Ouellet
authors.forename: Isabelle
authors.initials: I
authors.lastname: Plante
authors.forename: Vincent
authors.initials: V
authors.lastname: Boissonneault
authors.forename: Cherifa
authors.initials: C
authors.lastname: Ayari
authors.forename: Patrick
authors.initials: P
authors.lastname: Provost
mesh_terms: D001483:Base Sequence; D002460:Cell Line; D016174:Hepacivirus / Q000201:enzymology* / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D011485:Protein Binding / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000235:genetics; D034622:RNA Interference / Q000502:physiology; D012323:RNA Processing, Post-Transcriptional / Q000235:genetics*; D012335:RNA, Ribosomal / Q000235:genetics / Q000378:metabolism*; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism*; D043244:Ribonuclease III / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012270:Ribosomes / Q000201:enzymology*; D013379:Substrate Specificity / Q000235:genetics; D053586:Virus Internalization
chemical_list: D012335:RNA, Ribosomal; D012367:RNA, Viral; D043244:Ribonuclease III
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