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Access through your institution Buy or subscribe Synonymous mutations alter the sequence of a gene without changing the amino acid sequence of its encoded protein. Once thought to be
functionally ‘silent’, it is now known that synonymous mutations drive certain cancers, although the precise mechanisms are poorly understood. Lan et al. now show that synonymous mutations
can disrupt _N_6-methyladenosine (m6A) modifications – the most abundant type of eukaryotic mRNA modification – thereby influencing the stability of tumour suppressor mRNAs. To further
investigate the role of sm6A-DMs in cancer, the authors concentrated on sm6A-DMs found within _CDKN2A_ and _BRCA2_, tumour suppressor genes with exceptionally high observed rates of
sm6A-DMs. Epitranscriptome editing was used to increase or decrease methylation at specific m6A sites within these genes in different cancer cell lines. Upregulation of m6A levels resulted
in an increased abundance of _CDKN2A_ and _BRCA2_ mRNAs, whereas downregulation reduced mRNA levels. These findings underscore the importance of m6A methylation at these sites in the control
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during checkout ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support REFERENCES ORIGINAL ARTICLE * Lan, Y. et al.
Synonymous mutations promote tumorigenesis by disrupting m6A-dependent mRNA metabolism. _Cell_ https://doi.org/10.1016/j.cell.2025.01.026 (2025) Article PubMed Google Scholar Download
references AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Nature Reviews Molecular Cell Biology http://www.nature.com/nrm/ Michael Attwaters Authors * Michael Attwaters View author
publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to Michael Attwaters. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS
ARTICLE CITE THIS ARTICLE Attwaters, M. In tumour suppressors, synonymous is not always silent. _Nat Rev Mol Cell Biol_ 26, 254 (2025). https://doi.org/10.1038/s41580-025-00838-z Download
citation * Published: 03 March 2025 * Issue Date: April 2025 * DOI: https://doi.org/10.1038/s41580-025-00838-z SHARE THIS ARTICLE Anyone you share the following link with will be able to
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