Structure of the dengue virus RNA promoter
Open Access
- 24 June 2022
- journal article
- research article
- Published by Cold Spring Harbor Laboratory in RNA
- Vol. 28 (9), 1210-1223
- https://doi.org/10.1261/rna.079197.122
Abstract
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.Keywords
Funding Information
- NIH (1, R35 GM126942)
- National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services (HHSN272201700059C)
- Center for Cancer Research, National Cancer Institute (NCI) of National Institutes of Health
- NCI (75N91019D00024)
- the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research
- Department of Health and Human Services
- U.S. Government
- U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences (DE-AC02-06CH11357)
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