Figure 1.

Conceptual representation of molecular mechanisms affected by synonymous mutations. The orange oval denotes a synonymous mutation. (1) Interference with splicing could result in multiple outcomes, such as exon skipping, exon truncation, and retention of exons at higher rates. Exon skipping is illustrated here as the outcome with the most obvious impact on the mature mRNA sequence. (2) Synonymous mutations can affect the folded secondary structure of the mature transcript resulting in altered transcript stability. (3) Stability of the transcript can also be affected by synonymous mutations through their interference with RNA-binding proteins. (4) Synonymous mutations alter the codon, which can result in either increased or decreased translation rates depending on the relative abundance of the corresponding tRNA molecules in the cell; ultimately, co-translational folding may be affected, resulting in misfolded proteins. (5) Synonymous mutations can add or subtract miRNA binding sites, leading to altered levels of expression.