The Genomic 3′ UTR of Flaviviruses Is a Translation Initiation Enhancer
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 <i>Flavivirus</i> is a large group of positive, single-stranded RNA viruses that includes se...
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MDPI AG
2022-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/15/8604 |
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| author | Alfredo Berzal-Herranz Beatriz Berzal-Herranz Sara Esther Ramos-Lorente Cristina Romero-López |
| author_facet | Alfredo Berzal-Herranz Beatriz Berzal-Herranz Sara Esther Ramos-Lorente Cristina Romero-López |
| author_sort | Alfredo Berzal-Herranz |
| collection | DOAJ |
| description | 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 <i>Flavivirus</i> 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. |
| first_indexed | 2024-03-09T05:21:27Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T05:21:27Z |
| publishDate | 2022-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-a5b264bb5a744faebdb16ac5f796730a2023-12-03T12:40:52ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-08-012315860410.3390/ijms23158604The Genomic 3′ UTR of Flaviviruses Is a Translation Initiation EnhancerAlfredo Berzal-Herranz0Beatriz Berzal-Herranz1Sara Esther Ramos-Lorente2Cristina Romero-López3Instituto de Parasitología y Biomedicina “López-Neyra” (IPBLN), CSIC, PTS Granada, Avenida del Conocimiento 17, 18016 Armilla, Granada, SpainInstituto de Parasitología y Biomedicina “López-Neyra” (IPBLN), CSIC, PTS Granada, Avenida del Conocimiento 17, 18016 Armilla, Granada, SpainInstituto de Parasitología y Biomedicina “López-Neyra” (IPBLN), CSIC, PTS Granada, Avenida del Conocimiento 17, 18016 Armilla, Granada, SpainInstituto de Parasitología y Biomedicina “López-Neyra” (IPBLN), CSIC, PTS Granada, Avenida del Conocimiento 17, 18016 Armilla, Granada, SpainViruses 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 <i>Flavivirus</i> 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.https://www.mdpi.com/1422-0067/23/15/8604West Nile VirusWNVflavivirusregulation of translation3′ UTRcap-independent translation |
| spellingShingle | Alfredo Berzal-Herranz Beatriz Berzal-Herranz Sara Esther Ramos-Lorente Cristina Romero-López The Genomic 3′ UTR of Flaviviruses Is a Translation Initiation Enhancer International Journal of Molecular Sciences West Nile Virus WNV flavivirus regulation of translation 3′ UTR cap-independent translation |
| title | The Genomic 3′ UTR of Flaviviruses Is a Translation Initiation Enhancer |
| title_full | The Genomic 3′ UTR of Flaviviruses Is a Translation Initiation Enhancer |
| title_fullStr | The Genomic 3′ UTR of Flaviviruses Is a Translation Initiation Enhancer |
| title_full_unstemmed | The Genomic 3′ UTR of Flaviviruses Is a Translation Initiation Enhancer |
| title_short | The Genomic 3′ UTR of Flaviviruses Is a Translation Initiation Enhancer |
| title_sort | genomic 3 utr of flaviviruses is a translation initiation enhancer |
| topic | West Nile Virus WNV flavivirus regulation of translation 3′ UTR cap-independent translation |
| url | https://www.mdpi.com/1422-0067/23/15/8604 |
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