A cell line has a nonsense mutation in a critical gene, changing a UGG (Tryptophan) codon to a UGA (Stop) codon, which results in a non-functional truncated protein. A second, extragenic mutation is found to restore the gene's function. Which of the following is the most plausible mechanism for this suppression?
- A mutation in the gene for tryptophanyl-tRNA synthetase that alters its specificity.
- A frameshift mutation downstream of the nonsense codon that restores the original reading frame.
- A mutation that greatly increases the overall rate of translation for all cellular mRNAs.
- A mutation in the anticodon of a tRNA for Tryptophan (), changing it from 5'-CCA-3' to 5'-UCA-3'. (correct answer)
Explanation: This describes a nonsense suppressor tRNA. The wild-type tRNA^Trp has an anticodon 5'-CCA-3' which recognizes the 5'-UGG-3' codon for Tryptophan. A mutation in the tRNA gene that changes the anticodon to 5'-UCA-3' allows this modified tRNA to recognize the 5'-UGA-3' stop codon. The ribosome then inserts Tryptophan at the position of the nonsense mutation, allowing translation to continue and produce a full-length, functional protein. This is a classic example of extragenic (or intergenic) suppression.