Specific cleavage of Hepatitis C Virus RNA genome by human RNase P

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 A2860 as well as immunological and biochemical assays. Active cle...

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Detalles Bibliográficos
Autores: Nadal i Matamala, Anna, Martell Pérez-Alcalde, Maria, Lytle, J. Robin, Lyons, Alita J., Robertson, Hugh D., Cabot, Beatriz, Esteban, Juan I., Esteban, Rafael, Guardia, Jaime, Gómez, Jordi
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2002
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10256/25892
Acceso en línea:http://hdl.handle.net/10256/25892
Access Level:acceso abierto
Palabra clave:Virus de l'hepatitis C
Hepatitis C virus
Genomes virals
Viral genomes
Descripción
Sumario: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 A2860 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