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首页> 外文期刊>Nucleic Acids Research >Influence of correct secondary and tertiary RNA folding on the binding of cellular factors to the HCV IRES.
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Influence of correct secondary and tertiary RNA folding on the binding of cellular factors to the HCV IRES.

机译：正确的二级和三级RNA折叠对细胞因子与HCV IRES结合的影响。

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摘要

Structural integrity of the hepatitus C virus (HCV) 5' UTR region that includes the internal ribosome entry site (IRES) element is known to be essential for efficient protein synthesis. The functional explanation for this observation has been provided by the recent evidence that binding of several cellular factors to the HCV IRES is dependent on the conservation of its secondary structure. In order to better define the relationship between IRES activity, protein binding and RNA folding of the HCV IRES, we have focused our attention on its major stem-loop region (domain III) and the binding of several cellular factors: two subunits of eukaryotic initiation factor eIF3 and ribosomal protein S9. Our results show that binding of eIF3 p170 and p116/p110 subunits is dependent on the ability of the domain III apical stem-loop region to fold in the correct secondary structure whilst secondary structure of hairpin IIId is important for the binding of S9 ribosomal protein. In addition, we show that binding of S9 ribosomal protein also depends on the disposition of domain III on the HCV 5' UTR, indicating the presence of necessary inter-domain interactions required for the binding of this protein (thus providing the first direct evidence that tertiary folding of the HCV RNA does affect protein binding).
机译：已知包括内部核糖体进入位点（IRES）元素的丙型肝炎病毒（HCV）5'UTR区的结构完整性对于有效的蛋白质合成至关重要。最近的证据提供了对该观察结果的功能解释，即几种细胞因子与HCV IRES的结合取决于其二级结构的保守性。为了更好地定义HCV IRES的IRES活性，蛋白质结合和RNA折叠之间的关系，我们将注意力集中在其主要的茎-环区域（结构域III）和几种细胞因子的结合上：真核生物起始的两个亚基因子eIF3和核糖体蛋白S9。我们的结果表明，eIF3 p170和p116 / p110亚基的结合取决于结构域III根茎环区域在正确的二级结构中折叠的能力，而发夹IIId的二级结构对于S9核糖体蛋白的结合很重要。此外，我们显示S9核糖体蛋白的结合还取决于HCV 5'UTR上结构域III的位置，表明存在该蛋白结合所需的必要域间相互作用（因此提供了第一个直接证据， HCV RNA的三级折叠确实会影响蛋白质结合）。

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