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Assessment of Selective mRNA Translation in Mammalian Cells by Polysome Profiling
Published on: October 28, 2014
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Cancer-associated synonymous mutations reveal stress signal-dependent mRNA folding that selectively modulates protein
Sivakumar Vadivel Gnanasundram1,2, Lixiao Wang3, Sa Chen3
1Department of Medical Biosciences, Umea University, Umea 90185, Sweden robin.fahraeus@inserm.fr sivavg@iitpkd.ac.in.
RNA (New York, N.Y.)
|April 17, 2026
Summary
Cancer-associated synonymous mutations disrupt DNA damage-induced TP53 mRNA folding, altering p53 protein activity and gene expression. These mutations highlight a mechanism where mRNA structure influences protein function.
Area of Science:
- Molecular Biology
- Cancer Genomics
- RNA Structure
Background:
- Technical advances enable studying mRNA structure changes in response to signaling pathways.
- The impact of mRNA structure on encoded protein function is not well understood.
Purpose of the Study:
- Investigate how cancer-associated synonymous mutations (CASMs) affect TP53 mRNA structure and p53 protein function.
- Determine if CASMs interfere with signal-induced mRNA folding and subsequent protein activity.
Main Methods:
- In-cell RNA structural probing (SHAPE-MaP) to analyze mRNA folding.
- Transcript and chromatin immunoprecipitation (ChIP) analysis.
- Transcriptome analysis.
Main Results:
- Two CASMs (c.102 C>A and c.102 C>G) prevent DNA damage-induced TP53 mRNA folding.
- p53 from CASM34 exhibits reduced promoter binding and selective downstream gene induction (PUMA, 14-3-3-σ, but not p21CDKN1A).
- CASM34 globally attenuates DNA damage-responsive gene expression.
Conclusions:
- CASM34 interferes with signal-induced p53 mRNA folding during DNA damage, selectively modulating p53 activity.
- Cancer-associated synonymous mutations can target signal-induced mRNA structures to influence protein function.
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