- A suppressor is a second mutation that compensates for or alters the effects of a primary mutation.
- A nonsense suppressor is a gene coding for a mutant tRNA able to respond to one or more of the termination codons and insert an amino acid at that site.
- A missense suppressor codes for a tRNA that has been mutated so as to recognize a different codon. By inserting a different amino acid at a mutant codon, the tRNA suppresses the effect of the original mutation.
- A suppressor tRNA typically has a mutation in the anticodon that changes the codons to which it responds.
- When the new anticodon corresponds to a termination codon, an amino acid is inserted and the polypeptide chain is extended beyond the termination codon. This results in nonsense suppression at a site of nonsense mutation or in readthrough at a natural termination codon.
- Missense suppression occurs when the tRNA recognizes a different codon from usual, so that one amino acid is substituted for another.
Isolation of mutant tRNAs has been one of the most potent tools for analyzing the ability of a tRNA to respond to its codon(s) in mRNA, and for determining the effects that different parts of the tRNA molecule have on codon-anticodon recognition.
Mutant tRNAs are isolated by virtue of their ability to overcome the effects of mutations in genes coding for proteins. In general genetic terminology, a mutation that is able to overcome the effects of another mutation is called a suppressor.
In tRNA suppressor systems, the primary mutation changes a codon in an mRNA so that the protein product is no longer functional. The secondary, suppressor mutation changes the anticodon of a tRNA, so that it recognizes the mutant codon instead of (or as well as) its original target codon. The amino acid that is now inserted restores protein function. The suppressors are described as nonsense suppressors or missense suppressors, depending on the nature of the original mutation.
In a wild-type cell, a nonsense mutation is recognized only by a release factor, terminating protein synthesis. The suppressor mutation creates an aminoacyl-tRNA that can recognize the termination codon; by inserting an amino acid, it allows protein synthesis to continue beyond the site of nonsense mutation. This new capacity of the translation system allows a full-length protein to be synthesized, as illustrated in Figure 7.23. If the amino acid inserted by suppression is different from the amino acid that was originally present at this site in the wild-type protein, the activity of the protein may be altered.
Missense mutations change a codon representing one amino acid into a codon representing another amino acid, one that cannot function in the protein in place of the original residue. (Formally, any substitution of amino acids constitutes a missense mutation, but in practice it is detected only if it changes the activity of the protein.) The mutation can be suppressed by the insertion either of the original amino acid or of some other amino acid that is acceptable to the protein.
Figure 7.24 demonstrates that missense suppression can be accomplished in the same way as nonsense suppression, by mutating the anticodon of a tRNA carrying an acceptable amino acid so that it responds to the mutant codon. So missense suppression involves a change in the meaning of the codon from one amino acid to another.