Hambidge S J, Sarnow P
Department of Microbiology and Immunology, University of Colorado Health Sciences Center, Denver 80262.
Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10272-6. doi: 10.1073/pnas.89.21.10272.
Genetic and biochemical studies have revealed that the 5' noncoding region of poliovirus mediates translation of the viral mRNA by an unusual mechanism involving entry of ribosomes in internal sequences of mRNA molecules. We have found that mRNAs bearing the 5' noncoding region of poliovirus were translated at an enhanced rate in poliovirus-infected mammalian cells at a time when translation of cellular mRNAs was not yet inhibited. This translational enhancement of the polioviral 5' noncoding region was mediated by the expression of virus-encoded polypeptide 2A. This indicates that 2A is a multifunctional protein involved directly or indirectly in the activation of viral mRNA translation, in addition to its known roles in viral polyprotein processing and in inhibition of cellular protein synthesis. Thus, 2A represents an activator of translation of a viral mRNA that is translated by an internal ribosome binding mechanism. A likely consequence of this role of 2A is the efficient translation of viral mRNAs early in the infectious cycle, when host cell mRNAs can still compete with viral mRNAs for the host cell translation apparatus.
遗传学和生物化学研究表明，脊髓灰质炎病毒的5'非编码区通过一种不同寻常的机制介导病毒mRNA的翻译，该机制涉及核糖体进入mRNA分子的内部序列。我们发现，携带脊髓灰质炎病毒5'非编码区的mRNA在脊髓灰质炎病毒感染的哺乳动物细胞中，在细胞mRNA翻译尚未受到抑制时，以更高的速率进行翻译。脊髓灰质炎病毒5'非编码区的这种翻译增强是由病毒编码的多肽2A的表达介导的。这表明2A是一种多功能蛋白，除了其在病毒多蛋白加工和抑制细胞蛋白合成中的已知作用外，还直接或间接参与病毒mRNA翻译的激活。因此，2A代表了一种通过内部核糖体结合机制进行翻译的病毒mRNA的翻译激活剂。2A这一作用的一个可能结果是，在感染周期早期，当宿主细胞mRNA仍能与病毒mRNA竞争宿主细胞翻译装置时，病毒mRNA能够有效翻译。
