ArticleProceedings of the National Academy of Sciences of the United States of America2023
Evolution of coronavirus frameshifting elements: Competing stem networks explain conservation and variability.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 27 citations in OpenAlex.
- Viral RNAs as Dual Graphs: Extending the Motif Universe of RNAs.bioRxiv : the preprint server for biology · 2026Article
- Open questions on viral frameshifting: Exploiting the structural plasticity of the frameshifting element for therapeutic intervention.Biophysical journal · 2026Review
- SARS-CoV-2 Antivirals Identified from Small Molecule Modulators of Programmed -1 Ribosomal Frameshifting.ACS infectious diseases · 2026Article
- RNA Structural Ensemble Determinants of -1 Programmed Ribosomal Frameshifting Efficiency Across Coronavirus Evolution.Journal of molecular biology · 2025Article
- Covalent Probes Reveal Small-Molecule Binding Pockets in Structured RNA and Enable Bioactive Compound Design.Journal of the American Chemical Society · 2025Article
- How large is the universe of RNA-like motifs? A clustering analysis of RNA graph motifs using topological descriptors.PLoS computational biology · 2025Article
- Conformational Analysis and Structure-Altering Mutations of the HIV-1 Frameshifting Element.International journal of molecular sciences · 2025Article
- Strategies and efforts in circumventing the emergence of antiviral resistance against conventional antivirals.npj antimicrobials and resistance · 2025Review
- A NovelViruses · 2025Article
- A yeast-based reverse genetics system to generate HCoV-OC43 reporter viruses encoding an eighth subgenomic RNA.Journal of virology · 2025Article
- Phase Space Invaders' podcast episode with Tamar Schlick: a trajectory from mathematics to biology.Biophysical reviews · 2025Article
- Heterogeneous and multiple conformational transition pathways between pseudoknots of the SARS-CoV-2 frameshift element.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Sarbecovirus programmed ribosome frameshift RNA element folding studied by NMR spectroscopy and comparative analyses.Nucleic acids research · 2024Article
- Abolished frameshifting for predicted structure-stabilizing SARS-CoV-2 mutants: implications to alternative conformations and their statistical structural analyses.RNA (New York, N.Y.) · 2024Article
- Ribonanza: deep learning of RNA structure through dual crowdsourcing.bioRxiv : the preprint server for biology · 2024Article
- Tying the knot: Unraveling the intricacies of the coronavirus frameshift pseudoknot.PLoS computational biology · 2024Article
- The application of single-molecule optical tweezers to study disease-related structural dynamics in RNA.Biochemical Society transactions · 2024Review
- Article
- Tertiary folds of the SL5 RNA from the 5' proximal region of SARS-CoV-2 and related coronaviruses.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Tertiary folds of the SL5 RNA from the 5' proximal region of SARS-CoV-2 and related coronaviruses.bioRxiv : the preprint server for biology · 2023Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
The frameshifting RNA element (FSE) in coronaviruses (CoVs) regulates the programmed -1 ribosomal frameshift (-1 PRF) mechanism common to many viruses. The FSE is of particular interest as a promising drug candidate. Its associated pseudoknot or stem loop structure is thought to play a large role in frameshifting and thus viral protein production. To investigate the FSE structural evolution, we use our graph theory-based methods for representing RNA secondary structures in the RNA-As-Graphs (RAG) framework to calculate conformational landscapes of viral FSEs with increasing sequence lengths for representative 10 Alpha and 13 Beta-CoVs. By following length-dependent conformational changes, we show that FSE sequences encode many possible competing stems which in turn favor certain FSE topologies, including a variety of pseudoknots, stem loops, and junctions. We explain alternative competing stems and topological FSE changes by recurring patterns of mutations. At the same time, FSE topology robustness can be understood by shifted stems within different sequence contexts and base pair coevolution. We further propose that the topology changes reflected by length-dependent conformations contribute to tuning the frameshifting efficiency. Our work provides tools to analyze virus sequence/structure correlations, explains how sequence and FSE structure have evolved for CoVs, and provides insights into potential mutations for therapeutic applications against a broad spectrum of CoV FSEs by targeting key sequence/structural transitions.
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Registered trials
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 OpenQuestion graph.