UGA premature termination codon (UGA PTC)

A UGA premature termination codon (PTC), also known as an opal nonsense mutation, is a site within a messenger RNA (mRNA) sequence where a mutation has converted a sense codon into a stop signal (UGA) before the natural end of the coding sequence (PMID: 22312126). This premature signal typically results in the production of truncated, non-functional proteins and triggers nonsense-mediated decay (NMD), a cellular surveillance mechanism that degrades the faulty mRNA to prevent the accumulation of potentially toxic truncated peptides (Nature Reviews Genetics, 2014). UGA PTCs are responsible for approximately 10-15% of individual cases of various genetic diseases, including cystic fibrosis and Duchenne muscular dystrophy (NCBI Bookshelf, NBK1332). Therapeutic strategies targeting UGA PTCs involve small molecules known as read-through agents or nonsense suppressors, such as ataluren or certain aminoglycosides (Journal of Medicinal Chemistry, 2014). These drugs interact with the ribosome to decrease the fidelity of codon recognition at the PTC, allowing the insertion of a near-cognate amino acid and the synthesis of a full-length, potentially functional protein (PNAS, 2013). The efficacy of these treatments is often influenced by the specific nucleotide context surrounding the UGA codon, which affects the baseline 'leakiness' of the stop signal (Nucleic Acids Research, 2017).

Other names

Opal premature stop codonUGA nonsense mutationPremature termination codonOpal codonTGA premature stop codon

Promotion of translational read-through by inducing the ribosome to skip the premature stop codon and incorporate a near-cognate amino acid, thereby restoring full-length protein production.