Instituto de Parasitología y Biomedicina "López-Neyra" (IPBLN), CSIC, PTS Granada, Avenida del Conocimiento 17, 18016 Armilla, Granada, Spain.
Int J Mol Sci. 2022 Aug 3;23(15):8604. doi: 10.3390/ijms23158604.
Viruses rely on the cellular machinery of host cells to synthesize their proteins, and have developed different mechanisms enabling them to compete with cellular mRNAs for access to it. The genus is a large group of positive, single-stranded RNA viruses that includes several important human pathogens, such as West Nile, Dengue and Zika virus. The genome of flaviviruses bears a type 1 cap structure at its 5' end, needed for the main translation initiation mechanism. Several members of the genus also use a cap-independent translation mechanism. The present work provides evidence that the WNV 5' end also promotes a cap-independent translation initiation mechanism in mammalian and insect cells, reinforcing the hypothesis that this might be a general strategy of flaviviruses. In agreement with previous reports, we show that this mechanism depends on the presence of the viral genomic 3' UTR. The results also show that the 3' UTR of the WNV genome enhances translation of the cap-dependent mechanism. Interestingly, WNV 3' UTR can be replaced by the 3' UTR of other flaviviruses and the translation enhancing effect is maintained, suggesting a molecular mechanism that does not involve direct RNA-RNA interactions to be at work. In addition, the deletion of specific structural elements of the WNV 3' UTR leads to increased cap-dependent and cap-independent translation. These findings suggest the 3' UTR to be involved in a fine-tuned translation regulation mechanism.
病毒依赖宿主细胞的细胞机制来合成它们的蛋白质，并开发了不同的机制，使它们能够与细胞 mRNA 竞争以获得对其的访问。 属是一组大型的正单链 RNA 病毒，包括几种重要的人类病原体，如西尼罗河病毒、登革热病毒和寨卡病毒。黄病毒的基因组在其 5' 末端具有类型 1 帽结构，这是主要翻译起始机制所必需的。该属的几个成员也使用帽非依赖性翻译机制。本工作提供的证据表明，WNV 的 5' 端也在哺乳动物和昆虫细胞中促进了帽非依赖性翻译起始机制，这加强了这可能是黄病毒的一般策略的假设。与之前的报道一致，我们表明这种机制依赖于病毒基因组 3' UTR 的存在。结果还表明，WNV 基因组的 3' UTR 增强了帽依赖性机制的翻译。有趣的是，WNV 3' UTR 可以被其他黄病毒的 3' UTR 取代，并且翻译增强效应得以维持，这表明起作用的是一种不涉及直接 RNA-RNA 相互作用的分子机制。此外，WNV 3' UTR 的特定结构元件的缺失导致帽依赖性和帽非依赖性翻译增加。这些发现表明 3' UTR 参与了精细的翻译调节机制。
