ArticleNucleic acids research2017
Tuning RNA folding and function through rational design of junction topology.
Article in Nucleic acids research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- RNA-KG v2.0: an RNA-centered Knowledge Graph with Properties.NAR genomics and bioinformatics · 2026Article
- A programmable ribozyme for RNA signal transduction.Nature communications · 2026Article
- Engineering of Small Ribozymes Acting on RNA: What is Needed to Make a New Function Work with an Existing Catalyst?Chembiochem : a European journal of chemical biology · 2025Review
- Hyper-swivel head domain motions are required for complete mRNA-tRNA translocation and ribosome resetting.Nucleic acids research · 2022Article
- Phased nucleotide inserts for sequencing low-diversity RNA samples from in vitro selection experiments.RNA (New York, N.Y.) · 2020Article
- Salt Dependence of A-Form RNA Duplexes: Structures and Implications.The journal of physical chemistry. B · 2019Article
- Programming Structured DNA Assemblies to Probe Biophysical Processes.Annual review of biophysics · 2019Review
- A multi-axial RNA joint with a large range of motion promotes sampling of an active ribozyme conformation.Nucleic acids research · 2019Article
- How the Conformations of an Internal Junction Contribute to Fold an RNA Domain.The journal of physical chemistry. B · 2018Article
- RNA Structural Dynamics As Captured by Molecular Simulations: A Comprehensive Overview.Chemical reviews · 2018Review
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
Structured RNAs such as ribozymes must fold into specific 3D structures to carry out their biological functions. While it is well-known that architectural features such as flexible junctions between helices help guide RNA tertiary folding, the mechanisms through which junctions influence folding remain poorly understood. We combine computational modeling with single molecule Förster resonance energy transfer (smFRET) and catalytic activity measurements to investigate the influence of junction design on the folding and function of the hairpin ribozyme. Coarse-grained simulations of a wide range of junction topologies indicate that differences in sterics and connectivity, independent of stacking, significantly affect tertiary folding and appear to largely explain previously observed variations in hairpin ribozyme stability. We further use our simulations to identify stabilizing modifications of non-optimal junction topologies, and experimentally validate that a three-way junction variant of the hairpin ribozyme can be stabilized by specific insertion of a short single-stranded linker. Combined, our multi-disciplinary study further reinforces that junction sterics and connectivity are important determinants of RNA folding, and demonstrates the potential of coarse-grained simulations as a tool for rationally tuning and optimizing RNA folding and function.
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Registered trials
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