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The Genomic 3' UTR of Flaviviruses Is a Translation Initiation Enhancer.

Alfredo Berzal-HerranzBeatriz Berzal-HerranzSara Esther Ramos-LorenteCristina Romero-López
Published in: International journal of molecular sciences (2022)
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 Flavivirus 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.
Keyphrases
  • zika virus
  • induced apoptosis
  • aedes aegypti
  • dengue virus
  • cell cycle arrest
  • sars cov
  • air pollution
  • copy number
  • dna methylation
  • cell death
  • nucleic acid
  • antimicrobial resistance