Premature termination codon (PTC) (PTC)

Premature termination codons (PTCs) are nonsense mutations that introduce a stop signal (UAA, UAG, or UGA) into the protein-coding region of an mRNA before the natural end of the transcript. These mutations typically result in the production of truncated, non-functional proteins and often trigger nonsense-mediated mRNA decay (NMD), which reduces the overall level of the transcript (Kurosaki et al., 2019). A particularly common source of these mutations is the transition of CGA arginine codons to UGA stop codons at CpG dinucleotides due to the deamination of 5-methylcytosine (Cooper & Youssoufian, 1988). PTCs are responsible for approximately 10-15% of all inherited genetic diseases, including cystic fibrosis and Duchenne muscular dystrophy (Welch et al., 2007). Therapeutic strategies targeting PTCs focus on nonsense suppression or read-through agents, such as ataluren or specialized aminoglycosides like ELX-02, which encourage the ribosome to skip the premature stop signal and insert a near-cognate amino acid (Crawford et al., 2020). This process allows the translation machinery to continue to the natural stop codon, thereby restoring the production of a full-length, functional protein.

Other names

Nonsense mutationPremature stop codonUGA nonsense codonCGA to UGA mutationNonsense-mediated decay substrate

Nonsense suppression (read-through) therapy, where small molecules interact with the ribosome to promote the insertion of a near-cognate tRNA at the premature stop codon, allowing translation to continue to the natural stop codon.