Unlocking the functional impact of cancer-derived synonymous mutations

Messenger RNA (mRNA) translation is an essential process for regulated gene expression, and dysfunctional translation causes several human diseases, including cancer.

Recent advancements in next-generation sequencing and cancer genomics have expanded the ever-growing list of cancer mutations, including under-researched synonymous mutations (SMs) that alter the RNA sequence but not the amino acid composition of the encoded proteins.

The proposed work intends to address the molecular mechanisms by which cancer-derived SMs affect the function of the encoded protein and drive cancer progression by employing the following approaches, using p53 and oncogenic mRNAs enriched with SMs as a model system. i) Employing in silico tools to screen the cancer-derived SMs. ii) Developing strategies for understanding how SMs alter the structure of mRNA in vivo. iii) Determine how cellular stress signaling pathways are linked with epi-transcriptomic modifications and mRNA structures. iv) To determine how SMs affect gene expression and exert cell biological effects and to comprehend the clinical relevance of SMs.

Overall, the findings of this study will shed light on the role of SMs in cancer progression; this is a novel area of research that will expand the current molecular prognostic markers and pave the way for new therapeutic approaches aimed at precision medicine.