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Nucleic Acids Research Advance Access originally published online on July 3, 2009
Nucleic Acids Research 2009 37(16):5498-5510; doi:10.1093/nar/gkp553
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Nucleic Acids Research, 2009, Vol. 37, No. 16 5498-5510
© 2009 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

RNA

In vitro characterization of a miR-122-sensitive double-helical switch element in the 5' region of hepatitis C virus RNA

Rosa Díaz-Toledano1,2, Ascensión Ariza-Mateos1, Alex Birk3, Belén Martínez-García1 and Jordi Gómez1,2,*

1Laboratorio de Arqueología del RNA, Departamento de Bioquímica y Biología Molecular, Instituto de Parasitología y Biomedicina ‘López Neyra’ Armilla 18100, Granada, Spain, 2CIBERehd and 3Institute for Hepatitis and Virus Research, Doylestown, Pennsylvania, 18902, USA

*To whom correspondence should be addressed. Tel: 958181647; Fax: 958181632; Email: jgomez{at}ipb.csic.es

Received November 26, 2008. Revised June 12, 2009. Accepted June 12, 2009.

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.


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