In vitro characterization of a miR-122-sensitive double-helical switch element in the 5' region of hepatitis C virus RNA.
It has been proposed that the hepatitis C virus (HCV) internal ribosome entry site (IRES) resides within a locked conformation, owing to annealing of its immediate flanking sequences. In this study, structure probing using Escherichia coli dsRNA-specific RNase III and other classical tools showed that this region switches to an open conformation triggered by the liver-specific microRNA, miR-122. This structural transition, observed in vitro, may be the mechanistic basis for the involvement of downstream IRES structural domain VI in translation, as well as providing a role of liver-specific miR-122 in HCV infection. In addition, the induced RNA switching at the 5' untranslated region could ultimately represent a new mechanism of action of micro-RNAs.
Díaz-Toledano
Rosa
R
Laboratorio de Arqueología del RNA, Departamento de Bioquímica y Biología Molecular, Instituto de Parasitología y Biomedicina López Neyra Armilla, 18100 Granada, Spain.
Ariza-Mateos
Ascensión
A
Birk
Alex
A
Martínez-García
Belén
B
Gómez
Jordi
J
D020121:5' Untranslated Regions; D001483:Base Sequence; D004591:Electrophoresis, Polyacrylamide Gel; D004722:Endoribonucleases / Q000378:metabolism; D004926:Escherichia coli / Q000201:enzymology; D016174:Hepacivirus / Q000235:genetics*; D007700:Kinetics; D035683:MicroRNAs / Q000737:chemistry*; D008969:Molecular Sequence Data; D009154:Mutation; D009690:Nucleic Acid Conformation; D012367:RNA, Viral / Q000737:chemistry* / Q000378:metabolism; D043244:Ribonuclease III / Q000378:metabolism; D006163:Ribonuclease T1 / Q000378:metabolism; D017423:Sequence Analysis, RNA
D020121:5' Untranslated Regions; D035683:MicroRNAs; D012367:RNA, Viral; D004722:Endoribonucleases; D043244:Ribonuclease III; C032825:ribonuclease V(1); D006163:Ribonuclease T1