Stop codon serves as a precise molecular signal that marks the termination of translation, indicating the exact point where a polypeptide chain should be released from the ribosome. That's why in the universal genetic code, these three-nucleotide sequences do not code for any amino acid; instead, they function as stop signals that halt the addition of residues and trigger the disassembly of the translation complex. Without this definitive "end of" marker, ribosomes would continue reading past the intended coding region, producing truncated or entirely nonfunctional proteins that could disrupt cellular homeostasis. The concept is fundamental to molecular biology, as it ensures that the genetic information encoded in mRNA is translated into a functional, full-length protein with the correct length and sequence.
The termination process begins when the ribosome, having traversed the coding sequence from the start codon AUG, encounters one of the three stop codons located at the 3' end of the open reading frame. These codons—UAA, UAG, and UGA—are recognized not by transfer RNA molecules, but by specialized proteins known as release factors. Which means in prokaryotes, release factor 1 (RF1) recognizes UAA and UAG, while release factor 2 (RF2) recognizes UAA and UGA. In eukaryotes and archaea, a single release factor, eRF1, can recognize all three stop codons with the assistance of eRF3, a GTPase that facilitates the release reaction. This distinction highlights the elegant conservation and divergence of translational machinery across domains of life.
Once a release factor binds to the stop codon in the ribosomal A site, it promotes the hydrolysis of the ester bond linking the newly synthesized polypeptide to the tRNA in the P site. This chemical reaction, called peptidyl transferase activity, liberates the free protein chain. In prokaryotes
