Specific cleavage of hepatitis C virus RNA genome by human RNase P
Nadal, Anna (Hospital Universitari Vall d'Hebron)
Martell, María (Hospital Universitari Vall d'Hebron)
Robin Lytle, J. (Weill Medical College of Cornell University)
Lyons, Alita J. (Weill Medical College of Cornell University)
Robertson, Hugh D. (Weill Medical College of Cornell University)
Cabot, Beatriz (Hospital Universitari Vall d'Hebron)
Esteban, Juan I. (Hospital Universitari Vall d'Hebron)
Esteban, Rafael (Hospital Universitari Vall d'Hebron)
Guardia, Jaime (Hospital Universitari Vall d'Hebron)
Gómez, Jordi (Hospital Universitari Vall d'Hebron)
Universitat Autònoma de Barcelona. Departament de Medicina

Data:	2002
Resum:	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 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.
Ajuts:	Ministerio de Ciencia y Tecnología SAF1999-0108 Ministerio de Ciencia y Tecnología BIO00-0347 Ministerio de Sanidad y Consumo FISS-01/1351
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Pathogens
Publicat a:	Journal of Biological Chemistry, Vol. 277 Núm. 34 (Aug. 2002) , p. 30606-30613, ISSN 0021-9258

DOI: 10.1074/jbc.M203595200

8 p, 1.2 MB

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