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 language | English |
|---|---|
| Pages (from-to) | 154-160 |
| Number of pages | 7 |
| Journal | Virus Genes |
| Volume | 37 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 2008 Oct 1 |
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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 journal › Article
}
TY - JOUR
T1 - Iron increases translation initiation directed by internal ribosome entry site of hepatitis C virus
AU - Cho, Hana
AU - Lee, Hyung Chul
AU - Jang, Sung Key
AU - Kim, Yoon Ki
PY - 2008/10/1
Y1 - 2008/10/1
N2 - 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.
AB - 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.
KW - Hepatitis C virus
KW - Internal ribosome entry site
KW - Iron
KW - Iron-responsive element
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UR - http://www.scopus.com/inward/citedby.url?scp=49849091690&partnerID=8YFLogxK
U2 - 10.1007/s11262-008-0250-0
DO - 10.1007/s11262-008-0250-0
M3 - Article
C2 - 18566883
AN - SCOPUS:49849091690
VL - 37
SP - 154
EP - 160
JO - Virus Genes
JF - Virus Genes
SN - 0920-8569
IS - 2
ER -