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Updated: Jun 20, 2025

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Probing RNA Structure with Dimethyl Sulfate Mutational Profiling with Sequencing In Vitro and in Cells
Published on: December 9, 2022
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Visualizing RNA structure ensembles by single-molecule correlated chemical probing
J Winston Arney1, Alain Laederach2, Kevin M Weeks1
1Department of Chemistry, University of North Carolina, Chapel Hill, NC 27599-3290, USA.
Current Opinion in Structural Biology
|July 18, 2024
Summary
Single-molecule correlated chemical probing (smCCP) reveals RNA structure ensembles, overcoming limitations of averaged models. This technique decodes RNA plasticity for biological function and disease targeting.
Area of Science:
- Molecular Biology
- Biochemistry
- Structural Biology
Background:
- RNA molecules fold into complex structures with distinct functional states.
- Traditional methods obscure the heterogeneity of RNA structure ensembles.
- Analyzing RNA structures within cells presents significant challenges.
Purpose of the Study:
- To provide an overview of single-molecule probing principles.
- To review current strategies for deconvoluting RNA structure ensembles.
- To discuss recent applications of these methods in biological systems.
Main Methods:
- Single-molecule correlated chemical probing (smCCP) enables measurement of RNA structure ensembles.
- Chemical probing experiments are efficiently executed to gather data.
- Ensemble deconvolution strategies are employed to analyze heterogeneous RNA structures.
Main Results:
- smCCP allows for the measurement and deconvolution of RNA structure ensembles.
- This approach overcomes the limitations of averaged or computationally modeled structures.
- Recent applications demonstrate the utility of smCCP in diverse biological systems.
Conclusions:
- smCCP is revolutionizing the understanding of RNA structure plasticity.
- RNA structure plasticity is crucial for responding to stimuli and altering gene function.
- Targeting specific RNA ensemble subsets holds potential for modulating disease-associated processes.
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