A 5' RNA element promotes dengue virus RNA synthesis on a circular genome.
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.
Filomatori
Claudia V
CV
Fundación Instituto Leloir, Buenos Aires C1405BWE, Argentina.
Lodeiro
Maria F
MF
Alvarez
Diego E
DE
Samsa
Marcelo M
MM
Pietrasanta
Lía
L
Gamarnik
Andrea V
AV
D003716:Dengue Virus / Q000235:genetics* / Q000502:physiology; D016679:Genome, Viral; D018625:Microscopy, Atomic Force; D009690:Nucleic Acid Conformation; D012367:RNA, Viral / Q000096:biosynthesis* / Q000737:chemistry; D012324:RNA-Dependent RNA Polymerase / Q000378:metabolism; D038621:Regulatory Sequences, Ribonucleic Acid / Q000502:physiology*; D017361:Viral Nonstructural Proteins / Q000378:metabolism; D014779:Virus Replication / Q000502:physiology*
C096041:NS5 protein, flavivirus; D012367:RNA, Viral; D038621:Regulatory Sequences, Ribonucleic Acid; D017361:Viral Nonstructural Proteins; D012324:RNA-Dependent RNA Polymerase