the stop codons

If the start codon is the capital letter that begins a sentence, the stop codons are the full stop that ends it. Without a clear 'stop', the ribosome would keep reading off the end of the message and produce a runaway, garbled protein. The stop codons tell the machine: the protein is finished; release it.

There are exactly three stop codons — UAA, UAG and UGA. What makes them different from the other sixty-one codons is that no transfer RNA normally carries an amino acid for them. So when one of these triplets rolls into the ribosome's decoding site, no tRNA fits. Instead, a protein called a release factor recognizes the stop codon, occupies the empty slot, and triggers the ribosome to cut the finished chain free from the last transfer RNA. The three stops are sometimes given old nicknames — UAA 'ochre', UAG 'amber', UGA 'opal' — leftovers from the genetics labs that discovered them.

Stop codons matter clinically. A mutation that turns an ordinary codon into a stop (a nonsense mutation) chops the protein short, often crippling it — this underlies diseases such as some forms of cystic fibrosis and beta-thalassemia. Cells even run a quality-control patrol, nonsense-mediated decay, that destroys mRNAs carrying a stop codon in the wrong place. Conversely, a mutation that removes a stop lets the ribosome read on too far, adding nonsense to the protein's tail.