Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
Nucleic Acids Res. 2011 Sep 1;39(16):7276-88. doi: 10.1093/nar/gkr427. Epub 2011 Jun 6.
Some viral and cellular messages use an alternative mechanism to initiate protein synthesis that involves internal recruitment of the ribosome to an internal ribosome entry site (IRES). The Dicistroviridae intergenic regions (IGR) have been studied as model IRESs to understand the mechanism of IRES-mediated translation. In this study, the in vivo activity of IGR IRESs were compared. Our analysis demonstrates that Class I and II IGR IRESs have comparable translation efficiency in yeast and that Class II is significantly more active in mammalian cells. Furthermore, while Class II IGR IRES activity was enhanced in yeast grown at a higher temperature, temperature did not affect IGR IRES activity in mammalian cells. This suggests that Class II IRESs may not function optimally with yeast ribosomes. Examination of chimeric IGR IRESs, established that the IRES strength and temperature sensitivity are mediated by the ribosome binding domain. In addition, the sequence of the first translated codon is also an important determinant of IRES activity. Our findings provide us with a comprehensive overview of IGR IRES activities and allow us to begin to understand the differences between Classes I and II IGR IRESs.
一些病毒和细胞信息使用一种替代机制来启动蛋白质合成，该机制涉及核糖体向内内部核糖体进入位点（IRES）募集。杆状病毒科基因间区（IGR）已被研究为模型 IRES，以了解 IRES 介导的翻译的机制。在这项研究中，比较了 IGR IRES 的体内活性。我们的分析表明，I 类和 II 类 IGR IRES 在酵母中的翻译效率相当，而 II 类在哺乳动物细胞中的活性显著更高。此外，虽然在较高温度下生长的酵母中，II 类 IGR IRES 的活性增强，但温度对哺乳动物细胞中 IGR IRES 的活性没有影响。这表明 II 类 IRES 可能不能与酵母核糖体最佳地发挥作用。对嵌合 IGR IRES 的检查表明，IRES 的强度和温度敏感性由核糖体结合结构域介导。此外，第一个翻译密码子的序列也是 IRES 活性的重要决定因素。我们的研究结果为我们提供了 IGR IRES 活性的全面概述，并使我们能够开始理解 I 类和 II 类 IGR IRES 之间的差异。
