ArticleRNA (New York, N.Y.)2014
High-throughput mutate-map-rescue evaluates SHAPE-directed RNA structure and uncovers excited states.
Article in RNA (New York, N.Y.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 62 citations in OpenAlex.
- De novo design of RNA pseudoknots with deep learning.bioRxiv : the preprint server for biology · 2026Article
- Investigating the interplay between RNA structural dynamics and RNA chemical probing experiments.Nucleic acids research · 2025Article
- RNA ensembles from in vitro to in vivo: Toward predictive models of RNA cellular function.Current opinion in structural biology · 2024Review
- Diversity of ribosomes at the level of rRNA variation associated with human health and disease.Cell genomics · 2024Article
- Structural and computational studies of HIV-1 RNA.RNA biology · 2024Review
- Dissecting the energetic architecture within an RNA tertiary structural motif via high-throughput thermodynamic measurements.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Programmable antivirals targeting critical conserved viral RNA secondary structures from influenza A virus and SARS-CoV-2.Nature medicine · 2022Article
- Mutate-and-chemical-shift-fingerprint (MCSF) to characterize excited states in RNA using NMR spectroscopy.Nature protocols · 2021Review
- U2 snRNA structure is influenced by SF3A and SF3B proteins but not by SF3B inhibitors.PloS one · 2021Article
- 2'-O-Methylation can increase the abundance and lifetime of alternative RNA conformational states.Nucleic acids research · 2020Article
- Folding heterogeneity in the essential human telomerase RNA three-way junction.RNA (New York, N.Y.) · 2020Article
- Accelerated cryo-EM-guided determination of three-dimensional RNA-only structures.Nature methods · 2020Article
- Comprehensive sequence-to-function mapping of cofactor-dependent RNA catalysis in the glmS ribozyme.Nature communications · 2020Article
- An RNA pseudoknot stimulates HTLV-1RNA (New York, N.Y.) · 2020Article
- RNA base-pairing complexity in living cells visualized by correlated chemical probing.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- RNA Dynamics by NMR Spectroscopy.Chembiochem : a European journal of chemical biology · 2019Review
- In silico survey of the central conserved regions in viroids of theRNA (New York, N.Y.) · 2019Article
- The roles of structural dynamics in the cellular functions of RNAs.Nature reviews. Molecular cell biology · 2019Review
- Dynamic ensemble of HIV-1 RRE stem IIB reveals non-native conformations that disrupt the Rev-binding site.Nucleic acids research · 2019Article
- High-throughput determination of RNA structures.Nature reviews. Genetics · 2018Review
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The three-dimensional conformations of noncoding RNAs underpin their biochemical functions but have largely eluded experimental characterization. Here, we report that integrating a classic mutation/rescue strategy with high-throughput chemical mapping enables rapid RNA structure inference with unusually strong validation. We revisit a 16S rRNA domain for which SHAPE (selective 2'-hydroxyl acylation with primer extension) and limited mutational analysis suggested a conformational change between apo- and holo-ribosome conformations. Computational support estimates, data from alternative chemical probes, and mutate-and-map (M(2)) experiments highlight issues of prior methodology and instead give a near-crystallographic secondary structure. Systematic interrogation of single base pairs via a high-throughput mutation/rescue approach then permits incisive validation and refinement of the M(2)-based secondary structure. The data further uncover the functional conformation as an excited state (20 ± 10% population) accessible via a single-nucleotide register shift. These results correct an erroneous SHAPE inference of a ribosomal conformational change, expose critical limitations of conventional structure mapping methods, and illustrate practical steps for more incisively dissecting RNA dynamic structure landscapes.
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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.