RNA chaperoning and intrinsic disorder in the core proteins of Flaviviridae

Nucleic Acids Res. 2008 Feb;36(3):712-25. doi: 10.1093/nar/gkm1051. Epub 2007 Nov 22.


RNA chaperone proteins are essential partners of RNA in living organisms and viruses. They are thought to assist in the correct folding and structural rearrangements of RNA molecules by resolving misfolded RNA species in an ATP-independent manner. RNA chaperoning is probably an entropy-driven process, mediated by the coupled binding and folding of intrinsically disordered protein regions and the kinetically trapped RNA. Previously, we have shown that the core protein of hepatitis C virus (HCV) is a potent RNA chaperone that can drive profound structural modifications of HCV RNA in vitro. We now examined the RNA chaperone activity and the disordered nature of core proteins from different Flaviviridae genera, namely that of HCV, GBV-B (GB virus B), WNV (West Nile virus) and BVDV (bovine viral diarrhoea virus). Despite low-sequence similarities, all four proteins demonstrated general nucleic acid annealing and RNA chaperone activities. Furthermore, heat resistance of core proteins, as well as far-UV circular dichroism spectroscopy suggested that a well-defined 3D protein structure is not necessary for core-induced RNA structural rearrangements. These data provide evidence that RNA chaperoning-possibly mediated by intrinsically disordered protein segments-is conserved in Flaviviridae core proteins. Thus, besides nucleocapsid formation, core proteins may function in RNA structural rearrangements taking place during virus replication.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Circular Dichroism
  • DNA / chemistry
  • Flaviviridae*
  • Molecular Chaperones / chemistry*
  • Molecular Chaperones / metabolism
  • Protein Denaturation
  • Protein Structure, Secondary
  • RNA / chemistry*
  • RNA, Catalytic / metabolism
  • RNA-Binding Proteins / chemistry
  • Viral Core Proteins / chemistry*
  • Viral Core Proteins / metabolism


  • Molecular Chaperones
  • RNA, Catalytic
  • RNA-Binding Proteins
  • Viral Core Proteins
  • hammerhead ribozyme
  • RNA
  • DNA