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Updated: Aug 5, 2026
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Probing RNA Structure with Dimethyl Sulfate Mutational Profiling with Sequencing In Vitro and in Cells
Published on: December 9, 2022
Probing the complexity of cellular RNA folding: Ensembles, intermediates, and isoforms
Anthony M Mustoe1, Danny Incarnato2
1Therapeutic Innovation Center (THINC), Verna and Marrs McLean Department of Biochemistry and Molecular Pharmacology, and Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
Current Opinion in Structural Biology
|August 3, 2026
Summary
New RNA chemical probing and sequencing methods reveal complex RNA folding landscapes in cells. These advances help understand RNA structure-function relationships and may lead to new RNA-targeting therapies.
Area of Science:
- Biochemistry
- Molecular Biology
- Genomics
Background:
- RNA molecules exhibit complex structural landscapes shaped by dynamic processes throughout their lifecycle.
- Understanding these intricate RNA structures is crucial for deciphering their biological functions.
- Current methods face challenges in fully resolving RNA structural heterogeneity within cells.
Purpose of the Study:
- To review recent technological advancements in measuring and analyzing RNA structures in vivo.
- To highlight how these technologies are revolutionizing the study of RNA folding and function.
- To discuss the implications of resolving RNA structural ensembles for therapeutic development.
Main Methods:
- RNA chemical probing techniques to map RNA structure.
- High-throughput sequencing for large-scale structural analysis.
- Computational deconvolution algorithms to interpret complex structural data.
- Long-read sequencing for isoform-specific structural determination.
- In vivo methods for capturing co-transcriptional folding intermediates.
Main Results:
- Recent technologies enable unprecedented resolution of RNA structural landscapes within cellular environments.
- Advances allow for distinguishing between different RNA isoforms and their specific structures.
- New methods capture transient, co-transcriptional RNA folding intermediates.
- The complexity of RNA folding is directly linked to diverse functional mechanisms.
Conclusions:
- Resolving RNA structural ensembles provides critical insights into RNA biochemistry and function.
- Future directions include improved probe development, sequencing technologies, and integrative modeling.
- High-resolution mapping of RNA structural heterogeneity offers potential for targeted therapeutic strategies.
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