A premature termination codon (PTC), also known as a nonsense codon, refers to a three-nucleotide sequence in messenger RNA (mRNA) that signals the termination of protein synthesis prematurely. This aberrant termination occurs within the coding region of the mRNA transcript, before the full length of the protein is synthesized.
Normally, the genetic code is read by ribosomes, which assemble amino acids into a polypeptide chain based on the instructions provided by the mRNA molecule. Termination codons, specifically UAA, UAG, and UGA, are recognized by release factors that initiate the dissociation of the ribosome from the mRNA and release the nascent polypeptide.
In cases where a PTC is encountered during translation, it can trigger the degradation of the mRNA molecule or result in the production of a truncated, nonfunctional protein. PTCs can arise due to mutations, such as nonsense mutations or insertions and deletions, that introduce a premature termination signal into the mRNA. The resulting premature termination of protein synthesis can have deleterious consequences for cellular function and can be associated with various genetic disorders, such as cystic fibrosis, muscular dystrophy, or β-thalassemia.
Understanding the mechanisms of premature termination codons has led to the development of therapeutic approaches that aim to overcome the negative effects of PTCs. These include the use of drugs known as read-through agents that suppress premature termination and enable the production of functional full-length proteins, leading to potential treatments for genetic diseases caused by PTCs.
