A cancer-associated TP53 synonymous mutation induces synthesis of the p53 isoform p53/47
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00209805%3A_____%2F25%3A00080374" target="_blank" >RIV/00209805:_____/25:00080374 - isvavai.cz</a>
Result on the web
<a href="https://www.nature.com/articles/s41416-025-03127-w" target="_blank" >https://www.nature.com/articles/s41416-025-03127-w</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1038/s41416-025-03127-w" target="_blank" >10.1038/s41416-025-03127-w</a>
Alternative languages
Result language
angličtina
Original language name
A cancer-associated TP53 synonymous mutation induces synthesis of the p53 isoform p53/47
Original language description
BACKGROUND: Synonymous mutations (SMs) change the mRNA nucleotide sequences without altering the corresponding amino acid sequence and are usually overlooked due to their perceived lack of influence on protein function. However, emerging reports suggest that SMs play a significant role in disease development and progression. METHODS: Whole exome sequencing, RNA-sequencing, and droplet digital PCR were performed to identify the SMs from the malignant glioma patients. MutaRNA was used to predict the effect of SMs on RNA structure in silico. SHAPE-MaP was performed to probe and assess the effect of SMs on RNA structure in-cellulo. RESULTS: Here, we report that a Cancer-Associated SM in TP53 codon valine 203 (CASM203) results in the induction of the alternative translation initiated p53 protein isoform, p47. In-cell high-throughput RNA structural mapping showed that CASM203 mimics the Protein Kinase RNA-Like ER Kinase (PERK)-mediated p53 mRNA secondary structure that induces p47 expression of during the unfolded protein response (UPR). CONCLUSIONS: Overall, the single gain-of-function SM mimics the UPR-mediated p53 stress response, by generating RNA secondary structures akin to the PERK-mediated p53 mRNA structural switch. This illustrates the link between RNA structures and cellular biology and underscores the importance of SMs in cancer biology and their potential to further refine genetic diagnostics.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10608 - Biochemistry and molecular biology
Result continuities
Project
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Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
British journal of cancer
ISSN
0007-0920
e-ISSN
1532-1827
Volume of the periodical
133
Issue of the periodical within the volume
7
Country of publishing house
US - UNITED STATES
Number of pages
6
Pages from-to
970-975
UT code for WoS article
001537797600001
EID of the result in the Scopus database
2-s2.0-105011718643