ArticleProceedings of the National Academy of Sciences of the United States of America2021
High-throughput dissection of the thermodynamic and conformational properties of a ubiquitous class of RNA tertiary contact motifs.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- Automated high-throughput selection of DNA aptamers using a common optical next-generation sequencer.Nucleic acids research · 2026Article
- Systematic analysis of cotranscriptional RNA folding using transcription elongation complex display.Nature communications · 2025Article
- RNA ensembles from in vitro to in vivo: Toward predictive models of RNA cellular function.Current opinion in structural biology · 2024Review
- Exploring the energetic and conformational properties of the sequence space connecting naturally occurring RNA tetraloop receptor motifs.RNA (New York, N.Y.) · 2024Article
- High-throughput determination of RNA tertiary contact thermodynamics by quantitative DMS chemical mapping.Nucleic acids research · 2024Article
- High-throughput biochemistry in RNA sequence space: predicting structure and function.Nature reviews. Genetics · 2023Review
- Massively Parallel Profiling of RNA-targeting CRISPR-Cas13d.bioRxiv : the preprint server for biology · 2023Article
- 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
- The promise of cryo-EM to explore RNA structural dynamics.Journal of molecular biology · 2022Review
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6 authors.
Funding
Abstract
Despite RNA's diverse secondary and tertiary structures and its complex conformational changes, nature utilizes a limited set of structural "motifs"-helices, junctions, and tertiary contact modules-to build diverse functional RNAs. Thus, in-depth descriptions of a relatively small universe of RNA motifs may lead to predictive models of RNA tertiary conformational landscapes. Motifs may have different properties depending on sequence and secondary structure, giving rise to subclasses that expand the universe of RNA building blocks. Yet we know very little about motif subclasses, given the challenges in mapping conformational properties in high throughput. Previously, we used "RNA on a massively parallel array" (RNA-MaP), a quantitative, high-throughput technique, to study thousands of helices and two-way junctions. Here, we adapt RNA-MaP to study the thermodynamic and conformational properties of tetraloop/tetraloop receptor (TL/TLR) tertiary contact motifs, analyzing 1,493 TLR sequences from different classes. Clustering analyses revealed variability in TL specificity, stability, and conformational behavior. Nevertheless, natural GAAA/11ntR TL/TLRs, while varying in tertiary stability by ∼2.5 kcal/mol, exhibited conserved TL specificity and conformational properties. Thus, RNAs may tune stability without altering the overall structure of these TL/TLRs. Furthermore, their stability correlated with natural frequency, suggesting thermodynamics as the dominant selection pressure. In contrast, other TL/TLRs displayed heterogenous conformational behavior and appear to not be under strong thermodynamic selection. Our results build toward a generalizable model of RNA-folding thermodynamics based on the properties of isolated motifs, and our characterized TL/TLR library can be used to engineer RNAs with predictable thermodynamic and conformational behavior.
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