title: The chaperone-like activity of the hepatitis C virus IRES and CRE elements regulates genome dimerization.
abstract: The RNA genome of the hepatitis C virus (HCV) establishes a network of long-distance RNA-RNA interactions that direct the progression of the infective cycle. This work shows that the dimerization of the viral genome, which is initiated at the dimer linkage sequence (DLS) within the 3'UTR, is promoted by the CRE region, while the IRES is a negative regulatory partner. Using differential 2'-acylation probing (SHAPE-dif) and molecular interference (HMX) technologies, the CRE activity was found to mainly lie in the critical 5BSL3.2 domain, while the IRES-mediated effect is dependent upon conserved residues within the essential structural elements JIIIabc, JIIIef and PK2. These findings support the idea that, along with the DLS motif, the IRES and CRE are needed to control HCV genome dimerization. They also provide evidences of a novel function for these elements as chaperone-like partners that fine-tune the architecture of distant RNA domains within the HCV genome.
authors.affiliation: Instituto de Parasitología y Biomedicina López-Neyra, IPBLN-CSIC, PTS Granada, Avda. del Conocimiento 17, 18016 Armilla, Granada, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Romero-López
authors.affiliation: Unidad de Genómica, Instituto de Parasitología y Biomedicina López-Neyra, IPBLN-CSIC, PTS Granada, Avda. del Conocimiento 17, 18016 Armilla, Granada, Spain.
authors.forename: Alicia
authors.initials: A
authors.lastname: Barroso-delJesus
authors.affiliation: Instituto de Parasitología y Biomedicina López-Neyra, IPBLN-CSIC, PTS Granada, Avda. del Conocimiento 17, 18016 Armilla, Granada, Spain.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Berzal-Herranz
mesh_terms: D020413:3' Untranslated Regions; D001483:Base Sequence; D004171:Diploidy; D016679:Genome, Viral; D016174:Hepacivirus / Q000235:genetics* / Q000378:metabolism; D022781:Hepatocytes / Q000473:pathology / Q000821:virology; D006801:Humans; D000067556:Internal Ribosome Entry Sites; D009690:Nucleic Acid Conformation; D010442:Peptide Chain Initiation, Translational; D012367:RNA, Viral / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D012270:Ribosomes / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication
chemical_list: D020413:3' Untranslated Regions; D000067556:Internal Ribosome Entry Sites; D012367:RNA, Viral