ArticleJournal of the American Chemical Society2021
To Knot or Not to Knot: Multiple Conformations of the SARS-CoV-2 Frameshifting RNA Element.
Article in Journal of the American Chemical Society, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed.
- VARIANT: Web Server for Decoding and Analyzing Viral Mutations at Genome and Protein Levels.Biophysical journal · 2026Article
- Viral RNAs as Dual Graphs: Extending the Motif Universe of RNAs.bioRxiv : the preprint server for biology · 2026Article
- Identification of conserved RNA regulatory switches in living cells using RNA secondary structure ensemble mapping and covariation analysis.Nature biotechnology · 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
- Lycorine Derivative Inhibits SARS-CoV-2 Replication by Reducing -1 Programmed Ribosomal Frameshifting via Targeting ZAP.MedComm · 2026Article
- Kinetic Traps in RNA Folding: Targeted Design of Frameshifting Element Mutants by Thermodynamic and Kinetic Analysis of the Chikungunya Virus.The journal of physical chemistry. B · 2026Article
- Topological data analysis and topological deep learning beyond persistent homology: a review.Artificial intelligence review · 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
- A Cascade of Conformational Switches in SARS-CoV-2 Frameshifting: Coregulation by Upstream and Downstream Elements.Biochemistry · 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
- High-throughput sequencing: a breakthrough in molecular diagnosis for precision medicine.Functional & integrative genomics · 2025Review
- Multi-scale Jones polynomial and persistent Jones polynomial for knot data analysis.AIMS mathematics · 2025Article
- CParty: hierarchically constrained partition function of RNA pseudoknots.Bioinformatics (Oxford, England) · 2024Article
- Tree polynomials identify a link between co-transcriptional R-loops and nascent RNA folding.PLoS computational biology · 2024Article
- The role of structure in regulatory RNA elements.Bioscience reports · 2024Review
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
The SARS-CoV-2 frameshifting RNA element (FSE) is an excellent target for therapeutic intervention against Covid-19. This small gene element employs a shifting mechanism to pause and backtrack the ribosome during translation between Open Reading Frames 1a and 1b, which code for viral polyproteins. Any interference with this process has a profound effect on viral replication and propagation. Pinpointing the structures adapted by the FSE and associated structural transformations involved in frameshifting has been a challenge. Using our graph-theory-based modeling tools for representing RNA secondary structures, "RAG" (RNA-As-Graphs), and chemical structure probing experiments, we show that the 3-stem H-type pseudoknot (3_6 dual graph), long assumed to be the dominant structure, has a viable alternative, an HL-type 3-stem pseudoknot (3_3) for longer constructs. In addition, an unknotted 3-way junction RNA (3_5) emerges as a minor conformation. These three conformations share Stems 1 and 3, while the different Stem 2 may be involved in a conformational switch and possibly associations with the ribosome during translation. For full-length genomes, a stem-loop motif (2_2) may compete with these forms. These structural and mechanistic insights advance our understanding of the SARS-CoV-2 frameshifting process and concomitant virus life cycle, and point to three avenues of therapeutic intervention.
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