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Targeting ribosome assembly on the HCV RNA using a small RNA molecule

Bhat, Prasanna and Gnanasundram, Sivakumar Vadivel and Mani, Prashant and Ray, Partho Sarothi and Sarkar, Debi P and Das, Saumitra (2012) Targeting ribosome assembly on the HCV RNA using a small RNA molecule. In: RNA Biology, 9 (8). pp. 1110-1119.

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Official URL: http://dx.doi.org/10.4161/rna.21208

Abstract

Translation initiation of hepatitis C virus (HCV) RNA is the initial obligatory step of the viral life cycle, mediated through the internal ribosome entry site (IRES) present in the 5'-untranslated region (UTR). Initiation on the HCV IRES is mediated by multiple structure-specific interactions between IRES RNA and host 40S ribosomal subunit. In the present study we demonstrate that the SLIIIef domain, in isolation from other structural elements of HCV IRES, retain the ability to interact with 40S ribosome subunit. A small RNA SLRef, mimicking the SLIIIef domain was found to interact specifically with human La protein and the ribosomal protein S5 and selectively inhibit HCV RNA translation. More importantly, SLRef RNA showed significant suppression of replication in HCV monocistronic replicon and decrease of negative strand synthesis in HCV cell culture system. Finally, using Sendai virus based virosome, the targeted delivery of SLRef RNA into mice liver succeeded in selectively inhibiting HCV IRES mediated translation in vivo.

Item Type: Journal Article
Publication: RNA Biology
Publisher: Landes Bioscience
Additional Information: Copyright for this article is belongs to Landes Bioscience.
Keywords: HCV IRES;translation inhibition;Sendai virosome;La autoantigen;ribosome assembly
Department/Centre: Division of Biological Sciences > Microbiology & Cell Biology
Date Deposited: 23 Nov 2012 06:25
Last Modified: 23 Nov 2012 06:25
URI: http://eprints.iisc.ac.in/id/eprint/45149

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