stop codon

Stop codons are one of the 64 codons in the genetic code but do not code for an amino acid; instead they signal translation termination. The three stop codons—UAA (ochre), UAG (amber), and UGA (opal)—are recognized not by tRNAs but by eukaryotic release factor (eRF1) or prokaryotic release factors (RF1, RF2), which enter the ribosomal A site and promote hydrolysis of the bond linking the polypeptide chain to the final tRNA, releasing the completed protein. Clinically, mutations that create a premature stop codon (nonsense mutations) result in a truncated, typically nonfunctional protein—examples include certain forms of beta-thalassemia (nonsense mutations in beta-globin gene) and Duchenne muscular dystrophy. Nonsense-mediated decay (NMD) is a surveillance pathway that degrades mRNAs containing premature stop codons to prevent translation of truncated proteins. Conversely, mutations that destroy a stop codon (read-through mutations) can lead to abnormally elongated proteins, as seen in some hemoglobin variants (e.g., Hb Constant Spring, where a stop codon mutation causes an elongated alpha-globin chain). Understanding stop codons is essential for grasping molecular mechanisms of genetic diseases and the mechanism of action of drugs like aminoglycosides, which can cause ribosomal misreading and occasionally promote read-through of premature stop codons (a strategy explored therapeutically in conditions like cystic fibrosis with certain nonsense mutations).