Comparison between the HCV IRES domain IV RNA structure and the Iron Responsive Element.
Comparison between the HCV IRES domain IV RNA structure and the Iron Responsive Element.
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DOI：
10.1186/1477-5751-8-4
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发表时间：
2009-02-18
期刊：
影响因子：
--
通讯作者：
Lott WB
中科院分区：
文献类型：
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作者：
Tumban E;Painter JM;Lott WB
慢性丙型肝炎病毒（HCV）感染患者血清铁蛋白和肝铁浓度经常升高，肝铁浓度已被用于预测对干扰素治疗的反应，但这些相关性尚不清楚。HCV基因组在其内部核糖体进入位点（IRES）结构域IV （dIV）中含有一个类似铁反应元件（IRE）的RNA结构。IRE是一种茎环结构，用于通过抑制核糖体结合或保护mRNA免受核酸酶降解来控制参与铁稳态的真核蛋白的表达。HCV结构位于40S核糖体亚基的结合位点，可能作为真正的IRE或通过IRE样机制发挥作用。电泳迁移位移分析表明，HCV IRES结构域IV结构在体外不与铁调控蛋白1 （IRP1）相互作用。系统的HCV IRES RNA突变表明，IRP1不能适应野生型HCV IRES dIV RNA结构的形状。HCV IRES dIV RNA结构不是真正的IRES。这种RNA结构是否通过ire样机制响应其他细胞信号，导致了细胞内铁浓度和HCV感染参数之间的相关性，这种可能性仍有待检验。
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. 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. 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.