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

Genes Dev. 2006 Aug 15;20(16):2238-49. doi: 10.1101/gad.1444206. Epub 2006 Aug 1.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Dengue Virus / genetics*
  • Dengue Virus / physiology
  • Genome, Viral*
  • Microscopy, Atomic Force
  • Nucleic Acid Conformation
  • RNA, Viral / biosynthesis*
  • RNA, Viral / chemistry
  • RNA-Dependent RNA Polymerase / metabolism
  • Regulatory Sequences, Ribonucleic Acid / physiology*
  • Viral Nonstructural Proteins / metabolism
  • Virus Replication / physiology*

Substances

  • NS5 protein, flavivirus
  • RNA, Viral
  • Regulatory Sequences, Ribonucleic Acid
  • Viral Nonstructural Proteins
  • RNA-Dependent RNA Polymerase