ArticleRNA (New York, N.Y.)2022
A conserved arginine in NS5 binds genomic 3' stem-loop RNA for primer-independent initiation of flavivirus RNA replication.
Article in RNA (New York, N.Y.), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 15 citations in OpenAlex.
- The RNA promoter for pathogenic orthoflaviviruses replication is universal and serves as target for viral inhibition.PLoS pathogens · 2026Article
- Evolutionary refinement of the ZIKV 5' UTR dictates a trade-off between RNA stability and promoter accessibility.NAR molecular medicine · 2026Article
- Article
- Structural and functional characterization of the SLA' structure at the 3' terminus of the Zika virus negative-strand intermediate.RNA (New York, N.Y.) · 2025Article
- Modes of action of a small molecule antiviral compound targeting yellow fever virus NS4B protein.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Article
- The Flavivirus Non-Structural Protein 5 (NS5): Structure, Functions, and Targeting for Development of Vaccines and Therapeutics.Vaccines · 2024Review
- Serotype-Specific Regulation of Dengue Virus NS5 Protein Subcellular Localization.ACS infectious diseases · 2024Article
- The myriad roles of RNA structure in the flavivirus life cycle.RNA biology · 2024Review
- Investigating RNA-RNA interactions through computational and biophysical analysis.Nucleic acids research · 2023Article
- Conserved RNA secondary structure in Cherry virus A 5'-UTR associated with translation regulation.Virology journal · 2022Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The commitment to replicate the RNA genome of flaviviruses without a primer involves RNA-protein interactions that have been shown to include the recognition of the stem-loop A (SLA) in the 5' untranslated region (UTR) by the nonstructural protein NS5. We show that DENV2 NS5 arginine 888, located within the carboxy-terminal 18 residues, is completely conserved in all flaviviruses and interacts specifically with the top-loop of 3'SL in the 3'UTR which contains the pentanucleotide 5'-CACAG-3' previously shown to be critical for flavivirus RNA replication. We present virological and biochemical data showing the importance of this Arg 888 in virus viability and de novo initiation of RNA polymerase activity in vitro. Based on our binding studies, we hypothesize that ternary complex formation of NS5 with 3'SL, followed by dimerization, leads to the formation of the de novo initiation complex that could be regulated by the reversible zipping and unzipping of
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