ArticleNucleic acids research2015
Molecular crowding overcomes the destabilizing effects of mutations in a bacterial ribozyme.
Article in Nucleic acids research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 30 citations in OpenAlex.
- Optimized periphery-core interface increases fitness of the Bacillus subtilis glmS ribozyme.Nucleic acids research · 2024Article
- Protocell Effects on RNA Folding, Function, and Evolution.Accounts of chemical research · 2024Article
- Periodic temperature changes drive the proliferation of self-replicating RNAs in vesicle populations.Nature communications · 2023Article
- The Metabolome Weakens RNA Thermodynamic Stability and Strengthens RNA Chemical Stability.Biochemistry · 2022Article
- Vesicle encapsulation stabilizes intermolecular association and structure formation of functional RNA and DNA.Current biology : CB · 2022Article
- Encapsulation of ribozymes inside model protocells leads to faster evolutionary adaptation.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- RNA contributions to the form and function of biomolecular condensates.Nature reviews. Molecular cell biology · 2021Review
- The roles of structural dynamics in the cellular functions of RNAs.Nature reviews. Molecular cell biology · 2019Review
- Structural Perspective on Revealing and Altering Molecular Functions of Genetic Variants Linked with Diseases.International journal of molecular sciences · 2019Review
- Optimal molecular crowding accelerates group II intron folding and maximizes catalysis.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Oligomerization of a Bimolecular Ribozyme Modestly Rescues its Structural Defects that Disturb Interdomain Assembly to Form the Catalytic Site.Journal of molecular evolution · 2018Article
- Adventures with RNA graphs.Methods (San Diego, Calif.) · 2018Review
- Lipid vesicles chaperone an encapsulated RNA aptamer.Nature communications · 2018Article
- Soft Interactions with Model Crowders and Non-canonical Interactions with Cellular Proteins Stabilize RNA Folding.Journal of molecular biology · 2018Article
- Opportunities and Challenges in RNA Structural Modeling and Design.Biophysical journal · 2017Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
The native structure of the Azoarcus group I ribozyme is stabilized by the cooperative formation of tertiary interactions between double helical domains. Thus, even single mutations that break this network of tertiary interactions reduce ribozyme activity in physiological Mg(2+) concentrations. Here, we report that molecular crowding comparable to that in the cell compensates for destabilizing mutations in the Azoarcus ribozyme. Small angle X-ray scattering, native polyacrylamide gel electrophoresis and activity assays were used to compare folding free energies in dilute and crowded solutions containing 18% PEG1000. Crowder molecules allowed the wild-type and mutant ribozymes to fold at similarly low Mg(2+) concentrations and stabilized the active structure of the mutant ribozymes under physiological conditions. This compensation helps explains why ribozyme mutations are often less deleterious in the cell than in the test tube. Nevertheless, crowding did not rescue the high fraction of folded but less active structures formed by double and triple mutants. We conclude that crowding broadens the fitness landscape by stabilizing compact RNA structures without improving the specificity of self-assembly.
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