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RNA Stability

RNA Stability

Intact DNA strands can be found in fossils, while scientists sometimes struggle to keep RNA intact under laboratory conditions. The structural variations between RNA and DNA underlie the differences in their stability and longevity. Because DNA is double-stranded, it is inherently more stable. The single-stranded structure of RNA is less stable but also more flexible and can form weak internal bonds. Additionally, most RNAs in the cell are relatively short, while DNA can be up to 250 million...

RNA Stability

RNA Stability

Intact DNA strands can be found in fossils, while scientists sometimes struggle to keep RNA intact under laboratory conditions. The structural variations between RNA and DNA underlie the differences in their stability and longevity. Because DNA is double-stranded, it is inherently more stable. The single-stranded structure of RNA is less stable but also more flexible and can form weak internal bonds. Additionally, most RNAs in the cell are relatively short, while DNA can be up to 250 million...

mRNA Stability and Gene Expression

mRNA Stability and Gene Expression

The structure and stability of mRNA molecules regulates gene expression, as mRNAs are a key step in the pathway from gene to protein. In eukaryotes, the half-life of mRNA varies from a few minutes up to several days. mRNA stability is essential in growth and development. The absence of the proteins regulating its stability, such as tristetraprolin in mice, can cause systemic issues, including bone marrow overgrowth, inflammation, and autoimmunity.
Cis-acting Elements involved in mRNA stability

mRNA Stability and Gene Expression

mRNA Stability and Gene Expression

The structure and stability of mRNA molecules regulates gene expression, as mRNAs are a key step in the pathway from gene to protein. In eukaryotes, the half-life of mRNA varies from a few minutes up to several days. mRNA stability is essential in growth and development. The absence of the proteins regulating its stability, such as tristetraprolin in mice, can cause systemic issues, including bone marrow overgrowth, inflammation, and autoimmunity.
Cis-acting Elements involved in mRNA stability

Nucleic Acid Structure

Nucleic Acid Structure

The pentose sugar in DNA is deoxyribose, while in RNA the pentose sugar is ribose. The difference between the sugars is the presence of the hydroxyl group on the ribose's second carbon and a hydrogen on the deoxyribose's second carbon. The phosphate residue attaches to the hydroxyl group of the 5′ carbon of one sugar and the hydroxyl group of the 3′ carbon of the sugar of the next nucleotide, which forms a 5′ to 3′ phosphodiester linkage.
DNA Structure
DNA has a double-helix structure. The...

Improving Translational Accuracy

Improving Translational Accuracy

Base complementarity between the three base pairs of mRNA codon and the tRNA anticodon is not a failsafe mechanism. Inaccuracies can range from a single mismatch to no correct base pairing at all. The free energy difference between the correct and nearly correct base pairs can be as small as 3 kcal/ mol. With complementarity being the only proofreading step, the estimated error frequency would be one wrong amino acid in every 100 amino acids incorporated. However, error frequencies observed in...

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Related Experiment Video

Updated: Jun 16, 2026

Probing RNA Structure with Dimethyl Sulfate Mutational Profiling with Sequencing In Vitro and in Cells

Probing RNA Structure with Dimethyl Sulfate Mutational Profiling with Sequencing In Vitro and in Cells

Published on: December 9, 2022

Fine-scale structural information substantially improves mRNA therapeutic stability prediction.

Soon Yi^1,2, Sara E Ali³, Yashrajsinh Jadeja³

¹Center for RNA Science and Therapeutics, School of Medicine, Case Western Reserve University, Cleveland, OH, USA.

Molecular Therapy. Nucleic Acids

|June 15, 2026

Summary

This summary is machine-generated.

Optimizing messenger RNA (mRNA) stability is crucial for vaccine development. New sequence metrics, including base-pairing log odds, improve stability predictions, leading to more reliable mRNA designs.

Keywords:

MT: bioinformatics RNA secondary structure RNA stability RNA therapeutics base pairing log odds base pairing probability computational prediction mRNA vaccines

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Last Updated: Jun 16, 2026

Probing RNA Structure with Dimethyl Sulfate Mutational Profiling with Sequencing In Vitro and in Cells

Probing RNA Structure with Dimethyl Sulfate Mutational Profiling with Sequencing In Vitro and in Cells

Published on: December 9, 2022

Comparative RNA Structure Analysis of Nascent and Mature Transcripts in Saccharomyces cerevisiae

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Published on: February 27, 2026

Using In Vitro and In-cell SHAPE to Investigate Small Molecule Induced Pre-mRNA Structural Changes

Using In Vitro and In-cell SHAPE to Investigate Small Molecule Induced Pre-mRNA Structural Changes

Published on: January 30, 2019

Area of Science:

Biochemistry
Molecular Biology
Bioinformatics

Background:

The efficacy of COVID-19 mRNA vaccines highlights the need for improved mRNA stability.
Current understanding of sequence metrics influencing mRNA stability in solution is incomplete.
RNA secondary structure is vital for stability, but optimal design metrics are not fully defined.

Purpose of the Study:

To identify sequence metrics that accurately predict mRNA in-solution stability.
To develop a more effective model for mRNA stability prediction compared to existing methods.

Main Methods:

Investigated the role of local structural variations using base-pairing log odds (LO).
Developed a regression model (STRAND) combining global and local sequence features.
Validated the model's performance against existing machine learning and deep learning approaches.

Main Results:

Base-pairing log odds offer fine-scale insights complementing global metrics for stability modeling.
The STRAND model, using four features, reduced prediction error by over 2-fold.
Achieved robust generalization across diverse mRNA contexts.

Conclusions:

The STRAND model provides a compact, interpretable, and accurate framework for predicting mRNA in-solution stability.
This advancement facilitates the design of more stable mRNA molecules for therapeutic and vaccine applications.