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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 Flavivirus is a large group of positive, single-stranded RNA viruses that includes several important hum...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9369090/ https://www.ncbi.nlm.nih.gov/pubmed/35955738 http://dx.doi.org/10.3390/ijms23158604 |
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author | Berzal-Herranz, Alfredo Berzal-Herranz, Beatriz Ramos-Lorente, Sara Esther Romero-López, Cristina |
author_facet | Berzal-Herranz, Alfredo Berzal-Herranz, Beatriz Ramos-Lorente, Sara Esther Romero-López, Cristina |
author_sort | Berzal-Herranz, Alfredo |
collection | PubMed |
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 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. |
format | Online Article Text |
id | pubmed-9369090 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-93690902022-08-12 The Genomic 3′ UTR of Flaviviruses Is a Translation Initiation Enhancer Berzal-Herranz, Alfredo Berzal-Herranz, Beatriz Ramos-Lorente, Sara Esther Romero-López, Cristina Int J Mol Sci Article 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. MDPI 2022-08-03 /pmc/articles/PMC9369090/ /pubmed/35955738 http://dx.doi.org/10.3390/ijms23158604 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Berzal-Herranz, Alfredo Berzal-Herranz, Beatriz Ramos-Lorente, Sara Esther Romero-López, Cristina The Genomic 3′ UTR of Flaviviruses Is a Translation Initiation Enhancer |
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 | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9369090/ https://www.ncbi.nlm.nih.gov/pubmed/35955738 http://dx.doi.org/10.3390/ijms23158604 |
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