ArticleProceedings of the National Academy of Sciences of the United States of America2004
Single-molecule enzymology of RNA: essential functional groups impact catalysis from a distance.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
78 citing papers in PubMed, 144 citations in OpenAlex.
- Rapid and improved surface passivation method for Single-Molecule experiments.Methods (San Diego, Calif.) · 2026Article
- Universal cold RNA phase transitions.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Fast and robust two-dimensional inverse Laplace transformation of single-molecule fluorescence lifetime data.Biophysical journal · 2021Article
- Local-to-global signal transduction at the core of a MnNature communications · 2019Article
- Probing RNA structure and interaction dynamics at the single molecule level.Methods (San Diego, Calif.) · 2019Review
- Dynamic Recruitment of Single RNAs to Processing Bodies Depends on RNA Functionality.Molecular cell · 2019Article
- Exploring the effects of cosolutes and crowding on the volumetric and kinetic profile of the conformational dynamics of a poly dA loop DNA hairpin: a single-molecule FRET study.Nucleic acids research · 2019Article
- A bio-hybrid DNA rotor-stator nanoengine that moves along predefined tracks.Nature nanotechnology · 2018Article
- 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
- Tuning RNA folding and function through rational design of junction topology.Nucleic acids research · 2017Article
- The Shine-Dalgarno sequence of riboswitch-regulated single mRNAs shows ligand-dependent accessibility bursts.Nature communications · 2016Article
- Quantifying the Assembly of Multicomponent Molecular Machines by Single-Molecule Total Internal Reflection Fluorescence Microscopy.Methods in enzymology · 2016Article
- Assembly and dynamics of the U4/U6 di-snRNP by single-molecule FRET.Nucleic acids research · 2015Article
- Cation-induced kinetic heterogeneity of the intron-exon recognition in single group II introns.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Native purification and labeling of RNA for single molecule fluorescence studies.Methods in molecular biology (Clifton, N.J.) · 2015Article
- Molecular crowding accelerates ribozyme docking and catalysis.Journal of the American Chemical Society · 2014Article
- 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
18 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The hairpin ribozyme is a minimalist paradigm for studying RNA folding and function. In this enzyme, two domains dock by induced fit to form a catalytic core that mediates a specific backbone cleavage reaction. Here, we have fully dissected its reversible reaction pathway, which comprises two structural transitions (docking/undocking) and a chemistry step (cleavage/ligation), by applying a combination of single-molecule fluorescence resonance energy transfer (FRET) assays, ensemble cleavage assays, and kinetic simulations. This has allowed us to quantify the effects that modifications of essential functional groups remote from the site of catalysis have on the individual rate constants. We find that all ribozyme variants show similar fractionations into effectively noninterchanging molecule subpopulations of distinct undocking rate constants. This leads to heterogeneous cleavage activity as commonly observed for RNA enzymes. A modification at the domain junction additionally leads to heterogeneous docking. Surprisingly, most modifications not only affect docking/undocking but also significantly impact the internal chemistry rate constants over a substantial distance from the site of catalysis. We propose that a network of coupled molecular motions connects distant parts of the RNA with its reaction site, which suggests a previously undescribed analogy between RNA and protein enzymes. Our findings also have broad implications for applications such as the action of drugs and ligands distal to the active site or the engineering of allostery into RNA.
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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.