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Structure of the dengue virus RNA promoter
Dengue virus, a single-stranded positive sense RNA virus, is the most prevalent mosquito-borne pathogen in the world. Like all RNA viruses, it uses conserved structural elements within its genome to control essential replicative steps. A 70 nt stem–loop RNA structure (called SLA), found at the 5′-en...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory Press
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9380747/ https://www.ncbi.nlm.nih.gov/pubmed/35750488 http://dx.doi.org/10.1261/rna.079197.122 |
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author | Sun, Yi-Ting Varani, Gabriele |
author_facet | Sun, Yi-Ting Varani, Gabriele |
author_sort | Sun, Yi-Ting |
collection | PubMed |
description | Dengue virus, a single-stranded positive sense RNA virus, is the most prevalent mosquito-borne pathogen in the world. Like all RNA viruses, it uses conserved structural elements within its genome to control essential replicative steps. A 70 nt stem–loop RNA structure (called SLA), found at the 5′-end of the genome of all flaviviruses, functions as the promoter for viral replication. This highly conserved structure interacts with the viral polymerase NS5 to initiate RNA synthesis. Here, we report the NMR structure of a monomeric SLA from dengue virus serotype 1, assembled to high-resolution from independently folded structural elements. The DENV1 SLA has an L-shaped structure, where the top and side helices are coaxially stacked, and the bottom helix is roughly perpendicular to them. Because the sequence is highly conserved among different flavivirus genomes, it is very likely that the three-dimensional fold and local structure of SLA are also conserved among flaviviruses and required for efficient replication. This work provides structural insight into the dengue promoter and provides the foundation for the discovery of new antiviral drugs that target this essential replicative step. |
format | Online Article Text |
id | pubmed-9380747 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Cold Spring Harbor Laboratory Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-93807472023-09-01 Structure of the dengue virus RNA promoter Sun, Yi-Ting Varani, Gabriele RNA Article Dengue virus, a single-stranded positive sense RNA virus, is the most prevalent mosquito-borne pathogen in the world. Like all RNA viruses, it uses conserved structural elements within its genome to control essential replicative steps. A 70 nt stem–loop RNA structure (called SLA), found at the 5′-end of the genome of all flaviviruses, functions as the promoter for viral replication. This highly conserved structure interacts with the viral polymerase NS5 to initiate RNA synthesis. Here, we report the NMR structure of a monomeric SLA from dengue virus serotype 1, assembled to high-resolution from independently folded structural elements. The DENV1 SLA has an L-shaped structure, where the top and side helices are coaxially stacked, and the bottom helix is roughly perpendicular to them. Because the sequence is highly conserved among different flavivirus genomes, it is very likely that the three-dimensional fold and local structure of SLA are also conserved among flaviviruses and required for efficient replication. This work provides structural insight into the dengue promoter and provides the foundation for the discovery of new antiviral drugs that target this essential replicative step. Cold Spring Harbor Laboratory Press 2022-09 /pmc/articles/PMC9380747/ /pubmed/35750488 http://dx.doi.org/10.1261/rna.079197.122 Text en © 2022 Sun and Varani; Published by Cold Spring Harbor Laboratory Press for the RNA Society https://creativecommons.org/licenses/by-nc/4.0/This article is distributed exclusively by the RNA Society for the first 12 months after the full-issue publication date (see http://rnajournal.cshlp.org/site/misc/terms.xhtml). After 12 months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) . |
spellingShingle | Article Sun, Yi-Ting Varani, Gabriele Structure of the dengue virus RNA promoter |
title | Structure of the dengue virus RNA promoter |
title_full | Structure of the dengue virus RNA promoter |
title_fullStr | Structure of the dengue virus RNA promoter |
title_full_unstemmed | Structure of the dengue virus RNA promoter |
title_short | Structure of the dengue virus RNA promoter |
title_sort | structure of the dengue virus rna promoter |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9380747/ https://www.ncbi.nlm.nih.gov/pubmed/35750488 http://dx.doi.org/10.1261/rna.079197.122 |
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