ArticleThe Journal of biological chemistry2020
Cotranslational folding stimulates programmed ribosomal frameshifting in the alphavirus structural polyprotein.
Article in The Journal of biological chemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
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Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.
- The life cycle of the alphaviruses: From an antiviral perspective.Antiviral research · 2023Pooled it
- RNAViruses · 2026Review
- Feedback from the Nascent Chain Triggers Ribosomal Frameshifting and Transcript Decay.bioRxiv : the preprint server for biology · 2025Article
- Venezuelan Equine Encephalitis Virus: Structural Biology, Vaccines, and Advances in Functional Antibodies.Vaccines · 2025Review
- Advances in Viroporin Function and Structure: A Comparative Analysis of Alphavirus 6K with Well-Characterized Viroporins.Viruses · 2025Review
- A BSL-2 chimeric system designed to screen SARS-CoV-2 E protein ion channel inhibitors.Journal of virology · 2025Article
- Pathogenicity and virulence of chikungunya virus.Virulence · 2024Review
- Ribosomal frameshifting selectively modulates the assembly, function, and pharmacological rescue of a misfolded CFTR variant.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Ribosomal Frameshifting Selectively Modulates the Assembly, Function, and Pharmacological Rescue of a Misfolded CFTR Variant.bioRxiv : the preprint server for biology · 2024Article
- Life under tension: the relevance of force on biological polymers.Biophysics reports · 2024Article
- Structural and Functional Insights into Viral Programmed Ribosomal Frameshifting.Annual review of virology · 2023Review
- Requirement of a functional ion channel for Sindbis virus glycoprotein transport, CPV-II formation, and efficient virus budding.PLoS pathogens · 2022Article
- Review
- Mutations at the Alphavirus E1'-E2 Interdimer Interface Have Host-Specific Phenotypes.Journal of virology · 2022Article
- Cell-Free Synthesis Strategies to Probe Co-translational Folding of Proteins Within Lipid Membranes.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Thinking Outside the Frame: Impacting Genomes Capacity by Programmed Ribosomal Frameshifting.Frontiers in molecular biosciences · 2022Review
- Coordination of -1 programmed ribosomal frameshifting by transcript and nascent chain features revealed by deep mutational scanning.Nucleic acids research · 2021Article
- Ribosome Elongation Kinetics of Consecutively Charged Residues Are Coupled to Electrostatic Force.Biochemistry · 2021Article
- The SARS-CoV-2 Programmed -1 Ribosomal Frameshifting Element Crystal Structure Solved to 2.09 Å Using Chaperone-Assisted RNA Crystallography.ACS chemical biology · 2021Article
- Membrane proteins enter the fold.Current opinion in structural biology · 2021Review
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Viruses maximize their genetic coding capacity through a variety of biochemical mechanisms, including programmed ribosomal frameshifting (PRF), which facilitates the production of multiple proteins from a single mRNA transcript. PRF is typically stimulated by structural elements within the mRNA that generate mechanical tension between the transcript and ribosome. However, in this work, we show that the forces generated by the cotranslational folding of the nascent polypeptide chain can also enhance PRF. Using an array of biochemical, cellular, and computational techniques, we first demonstrate that the Sindbis virus structural polyprotein forms two competing topological isomers during its biosynthesis at the ribosome-translocon complex. We then show that the formation of one of these topological isomers is linked to PRF. Coarse-grained molecular dynamics simulations reveal that the translocon-mediated membrane integration of a transmembrane domain upstream from the ribosomal slip site generates a force on the nascent polypeptide chain that scales with observed frameshifting. Together, our results indicate that cotranslational folding of this viral protein generates a tension that stimulates PRF. To our knowledge, this constitutes the first example in which the conformational state of the nascent polypeptide chain has been linked to PRF. These findings raise the possibility that, in addition to RNA-mediated translational recoding, a variety of cotranslational folding or binding events may also stimulate PRF.
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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.