A 5′ RNA element promotes dengue virus RNA synthesis on a circular genome

• Autores: Filomatori, C.V.; Lodeiro, M.F.; Alvarez, D.E.; Samsa, M.M.; Pietrasanta, L.; Gamarnik, A.V.
• Año de publicación: 2006
• Idioma: inglés
• Tipo de recurso: artículo
• Fuente: Genes Dev. 2006;20(16):2238-2249
• Materia: AFM; Flavivirus; RNA cyclization; RNA-dependent RNA polymerase; Viral RNA synthesis; article; controlled study; Dengue virus; genome; nonhuman; priority journal; RNA replication; RNA synthesis; RNA virus; atomic force microscopy; biosynthesis; chemistry; conformation; Dengue virus; genetics; metabolism; physiology; regulatory RNA sequence; virus genome; virus replication; Dengue virus; Flavivirus; RNA viruses; NS5 protein, flavivirus; RNA directed RNA polymerase; virus protein; virus RNA; Dengue Virus; Genome, Viral; Microscopy, Atomic Force; Nucleic Acid Conformation; Regulatory Sequences, Ribonucleic Acid; RNA Replicase; RNA, Viral; Viral Nonstructural Proteins; Virus Replication
• Institución: Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturales

The mechanisms of RNA replication of plus-strand RNA viruses are still unclear. Here, we identified the first promoter element for RNA synthesis described in a flavivirus. Using dengue virus as a model, we found that the viral RdRp discriminates the viral RNA by specific recognition of a 5′ element named SLA. We demonstrated that RNA-RNA interactions between 5′ and 3′ end sequences of the viral genome enhance dengue virus RNA synthesis only in the presence of an intact SLA. We propose a novel mechanism for minus-strand RNA synthesis in which the viral polymerase binds SLA at the 5′ end of the genome and reaches the site of initiation at the 3′ end via long-range RNA-RNA interactions. These findings provide an explanation for the strict requirement of dengue virus genome cyclization during viral replication. © 2006 by Cold Spring Harbor Laboratory Press.