RNA chaperoning and intrinsic disorder in the core proteins of Flaviviridae.
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.
Ivanyi-Nagy
Roland
R
LaboRetro INSERM #758, Ecole Normale Supérieure de Lyon, IFR 128 Biosciences Lyon-Gerland, 69364 Lyon Cedex 07, France.
Lavergne
Jean-Pierre
JP
Gabus
Caroline
C
Ficheux
Damien
D
Darlix
Jean-Luc
JL
D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry; D018067:Flaviviridae; D018832:Molecular Chaperones / Q000737:chemistry* / Q000378:metabolism; D011489:Protein Denaturation; D017433:Protein Structure, Secondary; D012313:RNA / Q000737:chemistry*; D016337:RNA, Catalytic / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000737:chemistry; D014758:Viral Core Proteins / Q000737:chemistry* / Q000378:metabolism
D018832:Molecular Chaperones; D016337:RNA, Catalytic; D016601:RNA-Binding Proteins; D014758:Viral Core Proteins; C427204:hammerhead ribozyme; D012313:RNA; D004247:DNA