title: Specific cleavage of hepatitis C virus RNA genome by human RNase P.
abstract: We have found that RNase P from HeLa cells specifically and efficiently cleaves hepatitis C virus (HCV) transcripts in vitro. The evidence includes identification of the 5'-phosphate polarity of the newly generated termini at position A(2860) as well as immunological and biochemical assays. Active cleavage has been shown in five dominant sequences of HCV "quasispecies" differing at or near the position of cleavage, demonstrating that this is a general property of HCV RNA. During the analysis, a second cleavage event was found in the 3' domain of the internal ribosome entry site. We have found that HCV RNA competitively inhibits pre-tRNA cleavage by RNase P, suggesting that HCV RNA has structural similarities to tRNA. This finding sets HCV apart from other pathogens causing serious human diseases and represents the first description of human RNase P-viral RNA cleavage. Here we discuss the possible meaning of these RNase P-accessible structures built into the viral genome and their possible role in vivo. Moreover, such structures within the viral genome might be vulnerable to attack by therapeutic strategies.
authors.affiliation: Servicio de Medicina Interna-Hepatologia, Area de Investigación Básica, Hospital Vall d'Hebrón, Paseo Vall d'Hebrón 119-129, Barcelona 08035, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Nadal
authors.forename: María
authors.initials: M
authors.lastname: Martell
authors.forename: J Robin
authors.initials: JR
authors.lastname: Lytle
authors.forename: Alita J
authors.initials: AJ
authors.lastname: Lyons
authors.forename: Hugh D
authors.initials: HD
authors.lastname: Robertson
authors.forename: Beatriz
authors.initials: B
authors.lastname: Cabot
authors.forename: Juan I
authors.initials: JI
authors.lastname: Esteban
authors.forename: Rafael
authors.initials: R
authors.lastname: Esteban
authors.forename: Jaime
authors.initials: J
authors.lastname: Guardia
authors.forename: Jordi
authors.initials: J
authors.lastname: Gómez
mesh_terms: D001483:Base Sequence; D004722:Endoribonucleases / Q000378:metabolism*; D016679:Genome, Viral; D006367:HeLa Cells; D016174:Hepacivirus / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D011233:Precipitin Tests; D012322:RNA Precursors / Q000378:metabolism; D016337:RNA, Catalytic / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012367:RNA, Viral / Q000737:chemistry / Q000378:metabolism*; D043262:Ribonuclease P
chemical_list: D012322:RNA Precursors; D016337:RNA, Catalytic; D012333:RNA, Messenger; D012367:RNA, Viral; D004722:Endoribonucleases; C468368:RPP14 protein, human; D043262:Ribonuclease P