The Genomic 3′ UTR of Flaviviruses Is a Translation Initiation Enhancer
Alfredo Berzal‐Herranz, Beatriz Berzal-Herranz, Sara Esther Ramos-Lorente, Cristina Romero‐López
Abstract
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.