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Updated: May 16, 2026
13:42
RNA Secondary Structure Prediction Using High-throughput SHAPE
Published on: May 31, 2013
Volatility in mRNA secondary structure as a design principle for antisense
Erik Johnson1, Ranjan Srivastava
1Department of Chemical, Materials and Biomolecular Engineering, University of Connecticut, Storrs, CT 06269, USA.
Nucleic Acids Research
|November 20, 2012
Summary
Predicting effective antisense sequences is challenging. A new computational method, GenAVERT, identifies volatile mRNA regions for better antisense targeting, improving design success and saving resources.
Area of Science:
- Molecular Biology
- Bioinformatics
- Biophysics
Background:
- Designing effective antisense sequences is a significant challenge in molecular biology.
- The secondary structure of mRNA is dynamic, existing in multiple suboptimal states.
- Understanding mRNA structure dynamics could improve antisense targeting and design.
Purpose of the Study:
- To develop and evaluate a computational framework (GenAVERT) for predicting efficacious antisense sequences.
- To test the hypothesis that volatile mRNA regions offer superior accessibility for antisense targeting.
- To provide a more efficient approach for antisense sequence design.
Main Methods:
- GenAVERT computational framework was developed.
- UNAFold and RNAforester were used to generate and compare suboptimal mRNA structures.
- Analysis focused on identifying regions with high structural volatility (intramolecular hydrogen bonding).
Main Results:
- GenAVERT identified highly volatile mRNA regions with potentially superior antisense target accessibility.
- Antisense sequences designed using the volatility hypothesis closely matched natural antisense target sites.
- The predicted sites aligned with artificial target sites that demonstrated efficient gene down-regulation.
Conclusions:
- mRNA structural volatility is a key factor for accessible antisense targeting.
- The GenAVERT framework offers a promising new strategy for effective antisense sequence design.
- This approach can significantly reduce the time, cost, and labor associated with antisense development.
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