- Each type of nonsense codon is suppressed by tRNAs with mutant anticodons.
- Some rare suppressor tRNAs have mutations in other parts of the molecule.
Nonsense suppressors fall into three classes, one for each type of termination codon. Figure 7.25 describes the properties of some of the best characterized suppressors.
The easiest to characterize have been amber suppressors. In E. coli, at least 6 tRNAs have been mutated to recognize UAG codons. All of the amber suppressor tRNAs have the anticodon CUA, in each case derived from wild type by a single base change. The site of mutation can be any one of the three bases of the anticodon, as seen from supD, supE, and supF. Each suppressor tRNA recognizes only the UAG codon, instead of its former codon(s). The amino acids inserted are serine, glutamine, or tyrosine, the same as those carried by the corresponding wild-type tRNAs.
Ochre suppressors also arise by mutations in the anticodon. The best known are supC and supG, which insert tyrosine or lysine in response to both ochre (UAA) and amber (UAG) codons. This conforms with the prediction of the wobble hypothesis that UAA cannot be recognized alone.
A UGA suppressor has an unexpected property. It is derived from tRNATrp, but its only mutation is the substitution of A in place of G at position 24. This change replaces a G·U pair in the D stem with an A·U pair, increasing the stability of the helix. The sequence of the anticodon remains the same as the wild type, CCA . So the mutation in the D stem must in some way alter the conformation of the anticodon loop, allowing CCA to pair with UGA in an unusual wobble pairing of C with A. The suppressor tRNA continues to recognize its usual codon, UGG.
A related response is seen with a eukaryotic tRNA. Bovine liver contains a tRNASer with the anticodon mCCA. The wobble rules predict that this tRNA should respond to the tryptophan codon UGG; but in fact it responds to the termination codon UGA. So it is possible that UGA is suppressed naturally in this situation.
The general importance of these observations lies in the demonstration that codon-anticodon recognition of either wild-type or mutant tRNA cannot be predicted entirely from the relevant triplet sequences, but is influenced by other features of the molecule.