Comparison between the HCV IRES domain IV RNA structure and the iron responsive element

Tumban, Ebenezer, Painter, Jenna M., & Lott, William B. (2009) Comparison between the HCV IRES domain IV RNA structure and the iron responsive element. Journal of Negative Results in Biomedicine, 8(4).

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Background: Serum ferritin and hepatic iron concentrations are frequently elevated in patients who are chronically infected with the hepatitis C virus (HCV), and hepatic iron concentration has been used to predict response to interferon therapy, but these correlations are not well understood. The HCV genome contains an RNA structure resembling an iron responsive element (IRE) in its internal ribosome entry site (IRES) structural domain IV (dIV). An IRE is a stem loop structure used to control the expression of eukaryotic proteins involved in iron homeostasis by either inhibiting ribosomal binding or protecting the mRNA from nuclease degradation. The HCV structure, located within the binding site of the 40S ribosomal subunit, might function as an authentic IRE or by an IRE-like mechanism.-----

Results: Electrophoretic mobility shift assays showed that the HCV IRES domain IV structure does not interact with the iron regulatory protein 1 (IRP1) in vitro. Systematic HCV IRES RNA mutagenesis suggested that IRP1 cannot accommodate the shape of the wild type HCV IRES dIV RNA structure.-----

Conclusion The HCV IRES dIV RNA structure is not an authentic IRE. The possibility that this RNA structure is responsible for the observed correlations between intracellular iron concentration and HCV infection parameters through an IRE-like mechanism in response to some other cellular signal remains to be tested.

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ID Code: 18614
Item Type: Journal Article
Refereed: Yes
Keywords: Hepatitis C Virus, Internal Ribosome Entry Site, RNA, Iron Responsive Element, Translation
DOI: 10.1186/1477-5751-8-4
ISSN: 1477-5751
Subjects: Australian and New Zealand Standard Research Classification > BIOLOGICAL SCIENCES (060000) > MICROBIOLOGY (060500) > Virology (060506)
Australian and New Zealand Standard Research Classification > BIOLOGICAL SCIENCES (060000) > GENETICS (060400) > Genome Structure and Regulation (060407)
Australian and New Zealand Standard Research Classification > CHEMICAL SCIENCE (030000) > MEDICINAL AND BIOMOLECULAR CHEMISTRY (030400) > Characterisation of Biological Macromolecules (030403)
Divisions: Past > QUT Faculties & Divisions > Faculty of Science and Technology
Current > Institutes > Institute of Health and Biomedical Innovation
Past > Schools > School of Life Sciences
Copyright Owner: Copyright 2009 the authors ; licensee BioMed Central Ltd.
Copyright Statement: This is an Open Access article distributed under the terms of the Creative Commons Attribution License (,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Deposited On: 08 Jul 2009 22:18
Last Modified: 29 Feb 2012 14:37

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