Evidence map›Paper›PMID 18988629›Full record

ArticleNucleic acids research2008

A rugged free energy landscape separates multiple functional RNA folds throughout denaturation.

Mark A Ditzler, David Rueda, Jingjie Mo, Kristina Håkansson, Nils G Walter

Abstract read
In one paragraph

Article in Nucleic acids research, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.

0numbers the graph read from it
0cells of the map it votes in
54citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

54 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Computational De Novo Design of Group II Introns Yields Highly Active Ribozymes.Chembiochem : a European journal of chemical biology · 2025
    Article
  5. Article
  6. Review
  7. Article
  8. Review
  9. Article
  10. Structural basis of rotavirus RNA chaperone displacement and RNA annealing.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  11. mRNA structural dynamics shape Argonaute-target interactions.Nature structural & molecular biology · 2020
    Article
  12. Article
  13. Article
  14. The Story of RNA Folding, as Told in Epochs.Cold Spring Harbor perspectives in biology · 2018
    Review
  15. Review
  16. Article
  17. 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 · 2015
    Article
  18. Article
  19. Molecular crowding accelerates ribozyme docking and catalysis.Journal of the American Chemical Society · 2014
    Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

Mark A DitzlerDepartment of Chemistry, University of Michigan, Ann Arbor, MI 48109, USA.
David Rueda
Jingjie Mo
Kristina Håkansson
Nils G Walter

Funding

U-turn of the Hepatitis Delta Virus RibozymeR01GM062357 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI WALTER, NILS G · 2001 to 2019
$5.8M
NIGMS NIH HHS GM62357NIGMS NIH HHS R01 GM062357
6 · The paper itself

Abstract

The dynamic mechanisms by which RNAs acquire biologically functional structures are of increasing importance to the rapidly expanding fields of RNA therapeutics and biotechnology. Large energy barriers separating misfolded and functional states arising from alternate base pairing are a well-appreciated characteristic of RNA. In contrast, it is typically assumed that functionally folded RNA occupies a single native basin of attraction that is free of deeply dividing energy barriers (ergodic hypothesis). This assumption is widely used as an implicit basis to interpret experimental ensemble-averaged data. Here, we develop an experimental approach to isolate persistent sub-populations of a small RNA enzyme and show by single molecule fluorescence resonance energy transfer (smFRET), biochemical probing and high-resolution mass spectrometry that commitment to one of several catalytically active folds occurs unexpectedly high on the RNA folding energy landscape, resulting in partially irreversible folding. Our experiments reveal the retention of molecular heterogeneity following the complete loss of all native secondary and tertiary structure. Our results demonstrate a surprising longevity of molecular heterogeneity and advance our current understanding beyond that of non-functional misfolds of RNA kinetically trapped on a rugged folding-free energy landscape.

Indexed as

Electrophoretic Mobility Shift AssayFluorescence Resonance Energy TransferMass SpectrometryModels, MolecularNucleic Acid ConformationNucleic Acid DenaturationRNA, Catalytichairpin ribozymeRNA, Catalytic

Identifiers

PMID18988629
PMCPMC2602785

What OpenQuestion holds

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Registered trials

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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.