In the age of computational biology, it is easy to envision the genetic code as a set of immutable instructions that the cell follows without exception. The recent discovery of ciliate (1, 2) and trypanosomatid (3) species in which all three stop codons, which normally act to terminate protein translation by the ribosome, encode amino acids instead is a reminder that decoding the information in messenger RNA (mRNA) depends on molecular factors that we do not entirely understand. In these organisms, stop codons specify amino acids by default, and termination of mRNA translation only occurs in close proximity to the polyadenylate [poly(A)] tail. How do these species differentiate “true” stop codons from identical ones that encode amino acids? The answers to this puzzle may provide insights into translation termination and gene regulation in all eukaryotes.
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