Iron increases translation initiation directed by internal ribosome entry site of hepatitis C virus

Hana Cho, Hyung Chul Lee, Sung Key Jang, Yoon Ki Kim

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Although increased liver iron in individuals with chronic hepatitis C virus (HCV) is associated with a poor response to interferon therapy, the underlying molecular mechanisms are poorly understood. In this study, we show that iron enhances the translation initiation mediated by the internal ribosome entry site (IRES) of HCV. We also demonstrate by UV cross-linking analysis that specific cellular proteins bind to HCV 5′ untranslated region (5′ UTR) in an iron-dependent manner. Notably, p85 and p110 are competed out for their binding to HCV 5′ UTR when excess amounts of iron-responsive element (IRE) competitor RNAs are treated. This indicates that at least these two factors are common proteins for binding to HCV 5′ UTR and IRE. Our results, taken together, suggest that intracellular iron modulates the iron sensing pathway and HCV IRES-dependent translation by changing the binding affinities of the common cellular factors to IRE and HCV IRES, respectively. As a consequence, the coordinated regulation of gene expression by intracellular iron could provide favorable conditions for HCV proliferation.

Original languageEnglish
Pages (from-to)154-160
Number of pages7
JournalVirus Genes
Volume37
Issue number2
DOIs
Publication statusPublished - 2008 Oct 1

Fingerprint

Hepacivirus
Iron
5' Untranslated Regions
Internal Ribosome Entry Sites
Gene Expression Regulation
Chronic Hepatitis C
Protein Binding
Interferons
RNA
Liver

Keywords

  • Hepatitis C virus
  • Internal ribosome entry site
  • Iron
  • Iron-responsive element

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Applied Microbiology and Biotechnology
  • Immunology
  • Virology

Cite this

Iron increases translation initiation directed by internal ribosome entry site of hepatitis C virus. / Cho, Hana; Lee, Hyung Chul; Jang, Sung Key; Kim, Yoon Ki.

In: Virus Genes, Vol. 37, No. 2, 01.10.2008, p. 154-160.

Research output: Contribution to journalArticle

Cho, Hana ; Lee, Hyung Chul ; Jang, Sung Key ; Kim, Yoon Ki. / Iron increases translation initiation directed by internal ribosome entry site of hepatitis C virus. In: Virus Genes. 2008 ; Vol. 37, No. 2. pp. 154-160.
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