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Cancer-associated synonymous mutations selectively target the p53 DNA damage response [ChIP-seq]

GSE282501 Homo sapiens Genome binding/occupancy profiling by high throughput sequencing 4 samples Submitted 2026/03/01 Platform GPL34284
Summary
Recent technical advances have facilitated studies on changes in mRNA structures in response to signaling pathways, but how mRNA structures relate to the function of the encoded protein remains poorly understood. Synonymous mutations (SMs) possess comparable oncogenic potential to missense mutations. Here we have taken advantage of two Cancer Associated SMs at codon 34 (CASM34) in the p53 mRNA to demonstrate the impact of the RNA structure on protein activity in response to DNA damage. In-cell RNA structural probing illustrates how CASM34s prevent DNA damage-induced p53 mRNA folding. Genome-wide transcriptomics show that CASM34 alters the expression of genes in the p53 DNA-damage response pathway. DNA ChIP-seq analysis reveals that p53 expressed from CASM34 has reduced promoter binding and reduced induction of p53 downstream target genes PUMA and 14-3-3-σ but not p21CDKN1A. These results demonstrate that CASM34s selectively target p53 activity towards downstream targets in the DNA damage response pathway by interfering with p53 mRNA folding.
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Direct links to NCBI, no account and no request form: the whole study as GSE282501_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 4 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1189036 and SRA study SRP546742. Searching any of these in the dataset finder brings you back here.

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