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Updated: Apr 16, 2026

Probing RNA Structure with Dimethyl Sulfate Mutational Profiling with Sequencing In Vitro and in Cells
Published on: December 9, 2022
From static to dynamic: the need for structural ensembles and a predictive model of RNA folding and function
Daniel Herschlag1, Benjamin E Allred2, Seshadri Gowrishankar3
1Department of Biochemistry, Beckman Center, B400, 279 W. Campus Dr. MC: 5307, Stanford University, Stanford, CA 94305, USA; Department of Chemistry, 333 Campus Drive, Mudd Building, Room 121, Stanford University, Stanford, CA 94305, USA; Department of Chemical Engineering, 443 Via Ortega, Room 129, Stanford University, Stanford, CA 94305, USA.
Understanding biological RNA requires quantitative predictions of molecular conformations. Characterizing simple RNA components reveals key insights into complex folding and function, crucial for future research.
Area of Science:
- Molecular Biology
- Biophysics
- Computational Biology
Background:
- Understanding biological RNA function necessitates moving beyond descriptive approaches to quantitative predictions of molecular conformations and behavior.
- Complex RNA systems can be understood by characterizing smaller, fundamental components like helix-junction-helix elements and tertiary motifs.
Purpose of the Study:
- To provide quantitative predictions of RNA molecular conformations and functional behavior.
- To characterize small RNA components that govern the behavior of complex biological RNA systems.
Main Methods:
- Utilizing state-of-the-art experimental and computational methods.
- Analyzing conformational ensembles of helix-junction-helix elements and tertiary motifs.
Main Results:
- Conformations of helix-junction-helix elements are restricted to a small region of the conformational ensemble.
- This restricted region is highly dependent on the junction's topology.
- The correct alignment of tertiary motifs represents a rare conformation within the overall RNA folding landscape.
Conclusions:
- Quantitative prediction of RNA folding and function is essential for understanding biological RNA systems.
- Continued development of experimental and computational methods is critical.
- Characterizing fundamental RNA components offers deep insights into complex RNA behavior.
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