ArticleProceedings of the National Academy of Sciences of the United States of America2014
Molecular-crowding effects on single-molecule RNA folding/unfolding thermodynamics and kinetics.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 1 of them a synthesis that pooled it.
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Who cites it
61 citing papers in PubMed, 1 synthesis or guideline pooled it, 164 citations in OpenAlex.
- Macromolecular Crowding in Cytoplasm and Cellular Organelles.Sub-cellular biochemistry · 2025Pooled it
- A passive protein environment offsets RNA folding energetics in cells.bioRxiv : the preprint server for biology · 2026Article
- Photoactivated Signaling Networks using DNA-Based Synthetic Organelles as Biomimetic Protocells.Angewandte Chemie (International ed. in English) · 2026Article
- Macromolecular crowding alters transcription: real-time measurements with SYBR Green II.Research square · 2026Article
- The cellular landscape of i-motifs: genomic insights, methodological challenges, and the road ahead.Genome biology · 2026Review
- Capturing Structure and Morphology in Responsive Microgels: From Intrinsic Free Energy to Collective Behavior.Macromolecules · 2025Article
- Comparative Analysis of Biochemical and Cellular Assay Conditions and the Need for a Buffer That Mimics Cytoplasmic Environments.Molecules (Basel, Switzerland) · 2025Review
- Macromolecular crowding has opposite effects on two critical sub-steps of transcription initiation.FEBS letters · 2024Article
- The disordered N-terminal tail of SARS-CoV-2 Nucleocapsid protein forms a dynamic complex with RNA.Nucleic acids research · 2024Article
- Ionic liquid-caged nucleic acids enable active folding-based molecular recognition with hydrolysis resistance.Nucleic acids research · 2024Article
- Molecular Crowding Facilitates Ribozyme-Catalyzed RNA Assembly.ACS central science · 2023Article
- Excluded Volume and Weak Interactions in Crowded Solutions Modulate Conformations and RNA Binding of an Intrinsically Disordered Tail.The journal of physical chemistry. B · 2023Article
- Crowded environments tune the fold-switching in metamorphic proteins.Communications chemistry · 2023Article
- Article
- Structurally Different Yet Functionally Similar: Aptamers Specific for the Ebola Virus Soluble Glycoprotein and GP1,2 and Their Application in Electrochemical Sensing.International journal of molecular sciences · 2023Article
- Crowding-induced phase separation and gelling by co-condensation of PEG in NPM1-rRNA condensates.Biophysical journal · 2023Article
- The biophysics of disordered proteins from the point of view of single-molecule fluorescence spectroscopy.Essays in biochemistry · 2022Article
- Comparative study of SARS-CoV-2 infection in different cell types: Biophysical-computational approach to the role of potential receptors.Computers in biology and medicine · 2022Article
- An anionic ligand snap-locks a long-range interaction in a magnesium-folded riboswitch.Nature communications · 2022Article
- Vesicle encapsulation stabilizes intermolecular association and structure formation of functional RNA and DNA.Current biology : CB · 2022Article
1 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
The effects of "molecular crowding" on elementary biochemical processes due to high solute concentrations are poorly understood and yet clearly essential to the folding of nucleic acids and proteins into correct, native structures. The present work presents, to our knowledge, first results on the single-molecule kinetics of solute molecular crowding, specifically focusing on GAAA tetraloop-receptor folding to isolate a single RNA tertiary interaction using time-correlated single-photon counting and confocal single-molecule FRET microscopy. The impact of crowding by high-molecular-weight polyethylene glycol on the RNA folding thermodynamics is dramatic, with up to ΔΔG° ∼ -2.5 kcal/mol changes in free energy and thus >60-fold increase in the folding equilibrium constant (Keq) for excluded volume fractions of 15%. Most importantly, time-correlated single-molecule methods permit crowding effects on the kinetics of RNA folding/unfolding to be explored for the first time (to our knowledge), which reveal that this large jump in Keq is dominated by a 35-fold increase in tetraloop-receptor folding rate, with only a modest decrease in the corresponding unfolding rate. This is further explored with temperature-dependent single-molecule RNA folding measurements, which identify that crowding effects are dominated by entropic rather than enthalpic contributions to the overall free energy change. Finally, a simple "hard-sphere" treatment of the solute excluded volume is invoked to model the observed kinetic trends, and which predict ΔΔG° ∼ -5 kcal/mol free-energy stabilization at excluded volume fractions of 30%.
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