ArticleRNA (New York, N.Y.)2010
Long-range tertiary interactions in single hammerhead ribozymes bias motional sampling toward catalytically active conformations.
Article in RNA (New York, N.Y.), 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 38 citations in OpenAlex.
- Systematic discovery of novel ribozymes with gene silencing properties from global deep-sea RNA viromes.Frontiers in microbiology · 2026Article
- Enhanced hammerhead ribozyme turnover rates: Reevaluating therapeutic space for small catalytic RNAs.Molecular therapy. Nucleic acids · 2025Article
- A hammerhead ribozyme selects mechanically stable conformations for catalysis against viral RNA.Communications biology · 2025Article
- Toehold-mediated strand displacement to measure released product from self-cleaving ribozymes.RNA (New York, N.Y.) · 2022Article
- Systematic Screening, Rational Development, and Initial Optimization of Efficacious RNA Silencing Agents for Human Rod Opsin Therapeutics.Translational vision science & technology · 2019Article
- Divalent ions tune the kinetics of a bacterial GTPase center rRNA folding transition from secondary to tertiary structure.RNA (New York, N.Y.) · 2018Article
- RNA Structural Dynamics As Captured by Molecular Simulations: A Comprehensive Overview.Chemical reviews · 2018Review
- Life under the Microscope: Single-Molecule Fluorescence Highlights the RNA World.Chemical reviews · 2018Review
- Soft Interactions with Model Crowders and Non-canonical Interactions with Cellular Proteins Stabilize RNA Folding.Journal of molecular biology · 2018Article
- Nucleobases Undergo Dynamic Rearrangements during RNA Tertiary Folding.Journal of molecular biology · 2016Article
- Self-assembly Controls Self-cleavage of HHR from ASBVd (-): a Combined SANS and Modeling Study.Scientific reports · 2016Article
- Engineering a ribozyme cleavage-induced split fluorescent aptamer complementation assay.Nucleic acids research · 2016Article
- Molecular crowding overcomes the destabilizing effects of mutations in a bacterial ribozyme.Nucleic acids research · 2015Article
- Native purification and labeling of RNA for single molecule fluorescence studies.Methods in molecular biology (Clifton, N.J.) · 2015Article
- Single-molecule tools for enzymology, structural biology, systems biology and nanotechnology: an update.Archives of toxicology · 2014Review
- Disparate HDV ribozyme crystal structures represent intermediates on a rugged free-energy landscape.RNA (New York, N.Y.) · 2014Article
- Single molecule fluorescence approaches shed light on intracellular RNAs.Chemical reviews · 2014Review
- Structural dynamics of a mitochondrial tRNA possessing weak thermodynamic stability.Biochemistry · 2014Article
- Single transcriptional and translational preQ1 riboswitches adopt similar pre-folded ensembles that follow distinct folding pathways into the same ligand-bound structure.Nucleic acids research · 2013Article
- Crystal structure of 3WJ core revealing divalent ion-promoted thermostability and assembly of the Phi29 hexameric motor pRNA.RNA (New York, N.Y.) · 2013Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Enzymes generally are thought to derive their functional activity from conformational motions. The limited chemical variation in RNA suggests that such structural dynamics may play a particularly important role in RNA function. Minimal hammerhead ribozymes are known to cleave efficiently only in ∼ 10-fold higher than physiologic concentrations of Mg(2+) ions. Extended versions containing native loop-loop interactions, however, show greatly enhanced catalytic activity at physiologically relevant Mg(2+) concentrations, for reasons that are still ill-understood. Here, we use Mg(2+) titrations, activity assays, ensemble, and single molecule fluorescence resonance energy transfer (FRET) approaches, combined with molecular dynamics (MD) simulations, to ask what influence the spatially distant tertiary loop-loop interactions of an extended hammerhead ribozyme have on its structural dynamics. By comparing hammerhead variants with wild-type, partially disrupted, and fully disrupted loop-loop interaction sequences we find that the tertiary interactions lead to a dynamic motional sampling that increasingly populates catalytically active conformations. At the global level the wild-type tertiary interactions lead to more frequent, if transient, encounters of the loop-carrying stems, whereas at the local level they lead to an enrichment in favorable in-line attack angles at the cleavage site. These results invoke a linkage between RNA structural dynamics and function and suggest that loop-loop interactions in extended hammerhead ribozymes-and Mg(2+) ions that bind to minimal ribozymes-may generally allow more frequent access to a catalytically relevant conformation(s), rather than simply locking the ribozyme into a single active state.
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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 OpenQuestion graph.