ArticleThe Journal of biological chemistry2011
Removal of covalent heterogeneity reveals simple folding behavior for P4-P6 RNA.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 34 citations in OpenAlex.
- Cooperativity and Allostery in RNA Systems.Methods in molecular biology (Clifton, N.J.) · 2021Review
- How to measure and evaluate binding affinities.eLife · 2020Article
- Local-to-global signal transduction at the core of a MnNature communications · 2019Article
- The Story of RNA Folding, as Told in Epochs.Cold Spring Harbor perspectives in biology · 2018Review
- Single-Molecule Fluorescence Reveals Commonalities and Distinctions among Natural and in Vitro-Selected RNA Tertiary Motifs in a Multistep Folding Pathway.Journal of the American Chemical Society · 2017Article
- Does Cation Size Affect Occupancy and Electrostatic Screening of the Nucleic Acid Ion Atmosphere?Journal of the American Chemical Society · 2016Article
- Kinetic and thermodynamic framework for P4-P6 RNA reveals tertiary motif modularity and modulation of the folding preferred pathway.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- The Shine-Dalgarno sequence of riboswitch-regulated single mRNAs shows ligand-dependent accessibility bursts.Nature communications · 2016Article
- Cation-Anion Interactions within the Nucleic Acid Ion Atmosphere Revealed by Ion Counting.Journal of the American Chemical Society · 2015Article
- Probing the kinetic and thermodynamic consequences of the tetraloop/tetraloop receptor monovalent ion-binding site in P4-P6 RNA by smFRET.Biochemical Society transactions · 2015Review
- 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
- Structural dynamics of a single-stranded RNA-helix junction using NMR.RNA (New York, N.Y.) · 2014Article
- Advances in methods for native expression and purification of RNA for structural studies.Current opinion in structural biology · 2014Review
- Thio effects and an unconventional metal ion rescue in the genomic hepatitis delta virus ribozyme.Biochemistry · 2013Article
- Role of ion valence in the submillisecond collapse and folding of a small RNA domain.Biochemistry · 2013Article
- Hidden complexity in the isomerization dynamics of Holliday junctions.Nature chemistry · 2012Article
- Review
- Ultraviolet shadowing of RNA can cause significant chemical damage in seconds.Scientific reports · 2012Article
- Single Molecule Analysis Research Tool (SMART): an integrated approach for analyzing single molecule data.PloS one · 2012Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
RNA folding landscapes have been described alternately as simple and as complex. The limited diversity of RNA residues and the ability of RNA to form stable secondary structures prior to adoption of a tertiary structure would appear to simplify folding relative to proteins. Nevertheless, there is considerable evidence for long-lived misfolded RNA states, and these observations have suggested rugged energy landscapes. Recently, single molecule fluorescence resonance energy transfer (smFRET) studies have exposed heterogeneity in many RNAs, consistent with deeply furrowed rugged landscapes. We turned to an RNA of intermediate complexity, the P4-P6 domain from the Tetrahymena group I intron, to address basic questions in RNA folding. P4-P6 exhibited long-lived heterogeneity in smFRET experiments, but the inability to observe exchange in the behavior of individual molecules led us to probe whether there was a non-conformational origin to this heterogeneity. We determined that routine protocols in RNA preparation and purification, including UV shadowing and heat annealing, cause covalent modifications that alter folding behavior. By taking measures to avoid these treatments and by purifying away damaged P4-P6 molecules, we obtained a population of P4-P6 that gave near-uniform behavior in single molecule studies. Thus, the folding landscape of P4-P6 lacks multiple deep furrows that would trap different P4-P6 molecules in different conformations and contrasts with the molecular heterogeneity that has been seen in many smFRET studies of structured RNAs. The simplicity of P4-P6 allowed us to reliably determine the thermodynamic and kinetic effects of metal ions on folding and to now begin to build more detailed models for RNA folding behavior.
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