ArticleScience advances2025
A conserved opal termination codon optimizes a temperature-dependent trade-off between protein production and processing in alphaviruses.
Article in Science advances, 2025. 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.
- O'nyong-nyong virus adaptive mutations in non-structural protein 1 and 3 enhance RNA replication and overcome FHL1 requirement.Emerging microbes & infections · 2026Article
- RNAViruses · 2026Review
- Concepts of RNA virus evolution for the design of better antiviral countermeasures.Nature reviews. Microbiology · 2026Review
- Alphavirus replicase and regulatory RNA elements in host interactions and viral vector engineering.Journal of virology · 2026Review
- Alphavirus nsP3 as a multifunctional orchestrator of virus-host interplay.Journal of virology · 2026Review
- Scanning the horizon: deep mutational scanning approaches in virology.Journal of virology · 2026Review
- A conserved in-frame stop codon acts as a multipotent defense mechanism in alphaviruses.Science advances · 2026Article
- The Sindbis virus nsP3 opal codon protects viral RNA and fitness by maintaining replication spherule integrity.bioRxiv : the preprint server for biology · 2025Article
- Identification of AMOTL2 as an antiviral factor that enhances the human type I interferon response against Zika virus.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Determinants of human versus mosquito cell entry by the Chikungunya virus envelope proteins.bioRxiv : the preprint server for biology · 2025Article
- Functional RNA Elements in Alphavirus Genomes.Current microbiology · 2025Review
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6 authors.
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Abstract
Most mosquito-transmitted alphaviruses encode a premature opal termination codon upstream of their viral polymerase. We show that the Sindbis virus (SINV) opal codon outperforms other stop codons in primate cells at 37°C due to optimal translational readthrough. However, increased readthrough of all stop codons reduces opal preference at 28°C in primate and mosquito cells. Opal also outperforms all sense codons because opal-to-sense substitutions lead to excess polyprotein production at 37°C, disrupting orderly polyprotein processing and production of viral genomic RNAs (gRNAs) required for virus production. Increased readthrough at 28°C dampens the fitness advantages of opal codons. Unexpectedly, we find that a naturally occurring SINV mutation restores sense-codon fitness by further delaying polyprotein processing, allowing adequate time to produce gRNAs. Similar temperature-dependent mechanisms occur in the distantly related dual-host alphavirus, Ross River virus. Our work highlights sophisticated strategies dual-host alphaviruses use to optimize replication in divergent temperatures through a single codon.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.