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.