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Nucleic Acids Research 2005 33(2):683-692; doi:10.1093/nar/gki215
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Published online 28 January 2005

© The Author 2005. Published by Oxford University Press. All rights reserved
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions{at}oupjournals.org.

Article

A hepatitis C virus (HCV) internal ribosome entry site (IRES) domain III–IV-targeted aptamer inhibits translation by binding to an apical loop of domain IIId

Kunio Kikuchi1,2, Takuya Umehara1,2, Kotaro Fukuda1,2, Atsushi Kuno2, Tsunemi Hasegawa2 and Satoshi Nishikawa1,*

1 Institute for Biological Resources and Functions, National Institute of Advanced Industrial Science and Technology (AIST) 1-1-1 Higashi Tsukuba, Ibaraki 305-8566, Japan 2 Faculty of Science, Yamagata University Yamagata 990-8560, Japan

*To whom correspondence should be addressed. Tel: +81 298 61 6085; Fax: +81 298 61 6159; Email: satoshi-nishikawa{at}aist.go.jp

Received September 9, 2004. Revised December 5, 2004. Accepted January 8, 2005.

The hepatitis C virus (HCV) has a positive single-stranded RNA genome, and translation starts within the internal ribosome entry site (IRES) in a cap-independent manner. The IRES is well conserved among HCV subtypes and has a unique structure consisting of four domains. We used an in vitro selection procedure to isolate RNA aptamers capable of binding to the IRES domains III–IV. The aptamers that were obtained shared the consensus sequence ACCCA, which is complementary to the apical loop of domain IIId that is known to be a critical region of IRES-dependent translation. This convergence suggests that domain IIId is preferentially selected in an RNA–RNA interaction. Mutation analysis showed that the aptamer binding was sequence and structure dependent. One of the aptamers inhibited translation both in vitro and in vivo. Our results indicate that domain IIId is a suitable target site for HCV blockage and that rationally designed RNA aptamers have great potential as anti-HCV drugs.

Present address: Atsushi Kuno, Research Center for Glycoscience, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki 305-8568

The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors


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