Premature termination codon in mutant mRNA (PTC) (PTC)

Premature termination codons (PTCs) are nonsense mutations that occur within the protein-coding region of a messenger RNA (mRNA), leading to the premature cessation of translation (National Center for Biotechnology Information, 2023). This process typically results in the synthesis of truncated, non-functional proteins and often triggers nonsense-mediated mRNA decay (NMD), a cellular surveillance mechanism that degrades PTC-containing transcripts to prevent the accumulation of potentially toxic truncated products (Nature Reviews Molecular Cell Biology, 2019). PTCs are implicated in a wide range of genetic disorders, accounting for roughly 10% to 15% of all cases of inherited diseases such as cystic fibrosis, Duchenne muscular dystrophy, and various metabolic syndromes (Journal of Medical Genetics, 2021). Therapeutic intervention focuses on "translational read-through," where small molecules interact with the ribosome to decrease the fidelity of codon recognition at the PTC site (European Medicines Agency, 2022). This allows for the insertion of a near-cognate amino acid and the continuation of translation to produce a full-length, functional protein (PubMed, 2020). While drugs like ataluren and aminoglycoside derivatives have shown promise, balancing the restoration of protein function with the risk of read-through at natural stop codons remains a significant pharmacological challenge (Frontiers in Genetics, 2022).

Other names

Nonsense mutationPremature stop codonIn-frame stop codonPTC-containing mRNA

Induction of translational read-through by promoting the incorporation of near-cognate aminoacyl-tRNAs at the premature stop codon site, bypassing the termination signal to produce full-length protein (PubMed, 2020; EMA, 2022).