premature stop codon

Meaning: A premature stop codon is a UAA, UAG, or UGA in the mRNA reading frame that appears before the normal end of the coding sequence. No tRNA matches these codons, so release factors bind the A site and the polypeptide is released early, giving a truncated protein. The usual cause is a nonsense mutation, a point mutation that turns a sense codon into a stop (UAC for Tyr becoming UAA). An insertion or deletion that is not a multiple of three bases can also shift the frame and expose a stop downstream.

On the MCAT: Given a sequence with a point mutation, translate both versions and classify the change as silent, missense, or nonsense. A stop codon early in the sequence removes more of the protein than one near the 3′ end, so it is usually more damaging. A truncated product runs as a smaller band on SDS-PAGE, and an antibody to the C-terminal region may fail to detect it.

Common confusion: Nonsense is not missense. A missense mutation swaps one amino acid for another, while a nonsense mutation creates a stop signal and cuts the chain short. A silent mutation changes the codon but keeps the same amino acid.