Iron increases translation initiation directed by internal ribosome entry site of hepatitis C virus
Iron increases translation initiation directed by internal ribosome entry site of hepatitis C virus
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DOI：
10.1007/s11262-008-0250-0
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发表时间：
2008-10-01
期刊：
影响因子：
1.6
通讯作者：
Kim, Yoon Ki
中科院分区：
文献类型：
--
作者：
Cho, Hana;Lee, Hyung Chul;Kim, Yoon Ki
尽管慢性丙型肝炎病毒（HCV）患者肝脏铁含量增加与干扰素治疗反应不良有关，但其潜在的分子机制尚不清楚。在这项研究中，我们表明，铁增强的翻译起始介导的内部核糖体进入位点（IRES）的HCV。我们还通过紫外交联分析证明，特定的细胞蛋白以铁依赖的方式与HCV 5'非翻译区（5' UTR）结合。值得注意的是，当过量的铁响应元件（IRE）竞争RNA被处理时，p85和p110竞争与HCV 5'UTR的结合。这表明至少这两种因子是与HCV 5'UTR和IRE结合的共同蛋白。我们的研究结果表明，细胞内铁通过改变常见细胞因子对IRE和HCV IRES的结合亲和力，分别调节铁传感途径和HCV IRES依赖性翻译。因此，细胞内铁对基因表达的协调调节可以为HCV增殖提供有利条件。
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.