Inhibition of internal entry site (IRES)-mediated translation by a small yeast RNA: a novel strategy to block hepatitis C virus protein synthesis.

S. Das, M. Ott, A. Yamane, A. Venkatesan, Sanjeev Gupta, A. Dasgupta

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

The observation that poliovirus mRNA is not translated in the yeast Saccharomyces cerevisiae has led to the discovery of a small RNA (60 nt, called IRNA, inhibitor RNA) which was later shown to specifically inhibit internal ribosome entry site (IRES)-mediated translation of naturally uncapped mRNAs. Translation of cellular capped mRNAs was not significantly inhibited by IRNA. IRNA also specifically inhibited hepatitis C virus (HCV) IRES-mediated translation in vitro and in vivo. A hepatoma cell line constitutively expressing IRNA was refractory to infection by a chimeric poliovirus (PV/HCV) in which PV IRES is replaced by HCV-IRES. In contrast, a PV/EMCV chimeric virus containing the EMCV IRES was not significantly inhibited in the IRNA-hepatoma cell line compared to the control hepatoma cells. UV-crosslinking studies showed that the IRNA binds a number of cellular proteins that appear to be important for IRES-mediated translation. Interaction of these proteins with the viral IRES elements is believed to be important in recruiting ribosomes to the 5( UTR of viral RNAs. The binding of the purified La autoantigen to the HCV IRES element was efficiently and specifically competed by IRNA. These results provide a basis for development of novel drugs effective against HCV infection.

Original languageEnglish (US)
JournalFrontiers in Bioscience
Volume3
StatePublished - 1998
Externally publishedYes

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Viruses
Hepacivirus
Yeast
Yeasts
Virus Internalization
RNA
Encephalomyocarditis virus
Hepatocellular Carcinoma
Poliovirus
Proteins
Messenger RNA
Cell Line
Cells
5' Untranslated Regions
Viral RNA
Viral Proteins
Virus Diseases
Ribosomes
Saccharomyces cerevisiae
Crosslinking

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Inhibition of internal entry site (IRES)-mediated translation by a small yeast RNA : a novel strategy to block hepatitis C virus protein synthesis. / Das, S.; Ott, M.; Yamane, A.; Venkatesan, A.; Gupta, Sanjeev; Dasgupta, A.

In: Frontiers in Bioscience, Vol. 3, 1998.

Research output: Contribution to journalArticle

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