Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Universidad Autónoma de Madrid, Madrid, Spain.
PLoS One. 2011;6(10):e25699. doi: 10.1371/journal.pone.0025699. Epub 2011 Oct 7.
Poliovirus RNA utilizes eIF2 for the initiation of translation in cell free systems. Remarkably, we now describe that poliovirus translation takes place at late times of infection when eIF2 is inactivated by phosphorylation. By contrast, translation directed by poliovirus RNA is blocked when eIF2 is inactivated at earlier times. Thus, poliovirus RNA translation exhibits a dual mechanism for the initiation of protein synthesis as regards to the requirement for eIF2. Analysis of individual poliovirus non-structural proteins indicates that the presence of 2A(pro) alone is sufficient to provide eIF2 independence for IRES-driven translation. This effect is not observed with a 2A(pro) variant unable to cleave eIF4G. The level of 2A(pro) synthesized in culture cells is crucial for obtaining eIF2 independence. Expression of the N-or C-terminus fragments of eIF4G did not stimulate IRES-driven translation, nor provide eIF2 independence, consistent with the idea that the presence of 2A(pro) at high concentrations is necessary. The finding that 2A(pro) provides eIF2-independent translation opens a new and unsuspected area of research in the field of picornavirus protein synthesis.
脊髓灰质炎病毒 RNA 利用 eIF2 在无细胞系统中启动翻译。值得注意的是，我们现在描述了脊髓灰质炎病毒的翻译发生在感染后期，此时 eIF2 通过磷酸化失活。相比之下，当 eIF2 在早期失活时，由脊髓灰质炎病毒 RNA 指导的翻译被阻断。因此，脊髓灰质炎病毒 RNA 翻译在启动蛋白质合成方面针对 eIF2 的需求表现出双重机制。对单个脊髓灰质炎病毒非结构蛋白的分析表明，单独存在 2A(pro) 就足以提供 IRES 驱动翻译的 eIF2 独立性。具有不能切割 eIF4G 的 2A(pro) 变体的不存在这种效果。在培养细胞中合成的 2A(pro) 的水平对于获得 eIF2 独立性至关重要。eIF4G 的 N-或 C-末端片段的表达不能刺激 IRES 驱动的翻译，也不能提供 eIF2 独立性，这与 2A(pro) 在高浓度下存在的想法一致，是必要的。发现 2A(pro) 提供 eIF2 独立的翻译为小核糖核酸病毒蛋白质合成领域的研究开辟了一个新的、意想不到的领域。
