ArticleJournal of molecular biology2014
Folding pathways of the Tetrahymena ribozyme.
Article in Journal of molecular biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 16 citations in OpenAlex.
- In vivo-like nearest neighbor parameters improve prediction of fractional RNA base-pairing in cells.Nucleic acids research · 2023Article
- The Metabolome Weakens RNA Thermodynamic Stability and Strengthens RNA Chemical Stability.Biochemistry · 2022Article
- Topological crossing in the misfoldedProceedings of the National Academy of Sciences of the United States of America · 2022Article
- Thoughts on how to think (and talk) about RNA structure.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Single-nucleotide control of tRNA folding cooperativity under near-cellular conditions.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- In vivo RNA structural probing of uracil and guanine base-pairing by 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC).RNA (New York, N.Y.) · 2019Article
- Glyoxals as in vivo RNA structural probes of guanine base-pairing.RNA (New York, N.Y.) · 2018Article
- Capturing RNA Folding Free Energy with Coarse-Grained Molecular Dynamics Simulations.Scientific reports · 2017Article
- Nucleobases Undergo Dynamic Rearrangements during RNA Tertiary Folding.Journal of molecular biology · 2016Article
- Visualizing the formation of an RNA folding intermediate through a fast highly modular secondary structure switch.Nature communications · 2016Article
- Secondary structure encodes a cooperative tertiary folding funnel in the Azoarcus ribozyme.Nucleic acids research · 2016Article
- Bridging the gap between in vitro and in vivo RNA folding.Quarterly reviews of biophysics · 2016Article
- Exploiting post-transcriptional regulation to probe RNA structures in vivo via fluorescence.Nucleic acids research · 2015Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Like many structured RNAs, the Tetrahymena group I intron ribozyme folds through multiple pathways and intermediates. Under standard conditions in vitro, a small fraction reaches the native state (N) with kobs ≈ 0.6 min(-1), while the remainder forms a long-lived misfolded conformation (M) thought to differ in topology. These alternative outcomes reflect a pathway that branches late in folding, after disruption of a trapped intermediate (Itrap). Here we use catalytic activity to probe the folding transitions from Itrap to the native and misfolded states. We show that mutations predicted to weaken the core helix P3 do not increase the rate of folding from Itrap but they increase the fraction that reaches the native state rather than forming the misfolded state. Thus, P3 is disrupted during folding to the native state but not to the misfolded state, and P3 disruption occurs after the rate-limiting step. Interestingly, P3-strengthening mutants also increase native folding. Additional experiments show that these mutants are rapidly committed to folding to the native state, although they reach the native state with approximately the same rate constant as the wild-type ribozyme (~1 min(-1)). Thus, the P3-strengthening mutants populate a distinct pathway that includes at least one intermediate but avoids the M state, most likely because P3 and the correct topology are formed early. Our results highlight multiple pathways in RNA folding and illustrate how kinetic competitions between rapid events can have long-lasting effects because the "choice" is enforced by energy barriers that grow larger as folding progresses.
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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.