Codon optimality in cancer

Bushell, M. , Gillen, S. L. and Waldron, J. A. (2021) Codon optimality in cancer. Oncogene, 40, pp. 6309-6320. (doi: 10.1038/s41388-021-02022-x) (PMID:34584217)

Abstract

A key characteristic of cancer cells is their increased proliferative capacity, which requires elevated levels of protein synthesis. The process of protein synthesis involves the translation of codons within the mRNA coding sequence into a string of amino acids to form a polypeptide chain. As most amino acids are encoded by multiple codons, the nucleotide sequence of a coding region can vary dramatically without altering the polypeptide sequence of the encoded protein. Although mutations that do not alter the final amino acid sequence are often thought of as silent/synonymous, these can still have dramatic effects on protein output. Because each codon has a distinct translation elongation rate and can differentially impact mRNA stability, each codon has a different degree of ‘optimality’ for protein synthesis. Recent data demonstrates that the codon preference of a transcriptome matches the abundance of tRNAs within the cell and that this supply and demand between tRNAs and mRNAs varies between different cell types. The largest observed distinction is between mRNAs encoding proteins associated with proliferation or differentiation. Nevertheless, precisely how codon optimality and tRNA expression levels regulate cell fate decisions and their role in malignancy is not fully understood. This review describes the current mechanistic understanding on codon optimality, its role in malignancy and discusses the potential to target codon optimality therapeutically in the context of cancer.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Bushell, Professor Martin
• Authors: Bushell, M., Gillen, S. L., and Waldron, J. A.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Oncogene
• Publisher: Springer
• ISSN: 0950-9232
• ISSN (Online): 1476-5594
• Published Online: 28 September 2021
• Copyright Holders: Copyright © 2021 The Authors
• First Published: First published in Oncogene 40:6309–6320
• Publisher Policy: Reproduced under a Creative Commons licence