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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...

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Autores principales: Sun, Yi-Ting, Varani, Gabriele
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2022
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.
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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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