A nonsense mutation is a mutation that creates a translational stop codon in the coding sequence of a gene. The three chain-terminating codons, which are the normal stop signals for translation, are UGA, UAA, and UGA, called amber, ochre, and opal, respectively (although the latter is rarely used). Nonsense mutations are created by base substitutions at sense (coding) codons or by frameshift mutations, which usually create a nonsense codon 3′ to the frameshift.
Nonsense mutations are suppressed by mutant transfer RNAs that recognize the nonsense codon and insert their cognate amino acid into the polypeptide chain. Thus, nonsense mutations are a class of conditional lethal mutations. Because they occur in any gene but are suppressed by the same class of suppressors, nonsense mutations are a particularly powerful genetic tool. An elegant example was determining the life cycle of bacteriophage T4 (1). In addition, by using mutant tRNAs with known cognate amino acids, the functional significance of amino acid replacements at various positions in a protein can be determined (2). Most suppressor tRNAs are mutant in their anticodon, although mutations and modifications elsewhere in the molecule have suppressing effects. Indeed, the first UGA suppressor discovered is mutant outside of its anticodon. Mutations in other components of the translational machinery, such as the release factors and ribosomal subunits, also can suppress nonsense mutations (3).
Nonsense mutations can be polar, ie, can eliminate the expression of genes in the same operon encoded downstream from the mutation. The polarity of a nonsense mutation depends on its proximity to a codon that can restart translation. In Escherichia coli the polarity of many nonsense mutations can be suppressed by mutations in Rho, the transcriptional termination factor. Thus in these cases polarity is probably caused by inhibition of RNA polymerase by Rho when it interacts with untranslated mRNA (4).
