Altered Decoding by Transfer RNA May Cause Suppression

Nonsense mutations can be suppressed by alterations in tRNA. As discussed above, a nonsense mutation occurs when a codon that should code for an amino acid is changed to a stop codon. This results in a truncated and usually nonfunctional protein. Such a defect may be suppressed, at least partially, by changing the anticodon sequence of a tRNA molecule so that it recognizes the stop codon instead. Consider the stop codon UAG. Altering the anticodon of tRNAGln from GUC (reading CAG for Gln) to AUC will make it recognize UAG instead. Such an altered tRNA will insert glutamine wherever it finds a UAG stop codon (Fig. 13.26).

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Such altered tRNA molecules are known as suppressor tRNAs. The UAG stop codon is known as amber and the UAA stop codon as ochre. The UGA stop codon has no universally accepted name, but is sometimes called opal or umber. Amber suppressors are mutant tRNAs that read UAG instead of their original codon. Ochre suppressor tRNAs read both UAA and UAG due to wobble. Opal suppressors are rare.

Suppressor tRNA mutations can only occur if a cell has more than one tRNA that reads a particular codon. One may be mutated while the other must carry out the original function; otherwise, the loss of the original tRNA would be lethal. In practice, cells often have multiple tRNA genes and so suppressor mutations are reasonably common, at least in microorganisms. Bacterial suppressor mutations have been found in tRNAs for glutamine, leucine, serine, tyrosine and tryptophan. The amino acid inserted by the suppressor tRNA may be identical to the original amino acid whose codon mutated to give the stop codon. In this case, the protein made will be fully restored. Alternatively, a different amino acid may be inserted and a partially active protein may be produced.

Remember that stop codons are normally recognized by release factor, and have no cognate tRNAs. Since suppressor tRNA competes with release factor, suppression is never complete and typically ranges from 10 to 40 percent. This may provide enough of the suppressed protein for the cells to survive. However, the suppressor tRNA will also suppress other stop codons in the same cell and so generate longer (and incorrect) versions of many proteins whose genes were never mutated. Not surprisingly, cells with suppressor mutations grow more slowly. Only bacteria and lower eukaryotes (e.g., yeasts, roundworms) can tolerate suppressor mutations. In both insects and mammals, suppressor mutations are lethal.

Frameshift suppressor tRNAs are also occasionally found among bacteria. These mutant tRNA molecules have an enlarged anticodon loop and a four-base anticodon. This enables them to insert a single amino acid by reading four bases in the mRNA. They can suppress the effects of a frameshift mutation that was caused by the insertion of a single extra base. Frameshift suppressor tRNAs with five-base anticodons have been made artificially, but have not been isolated naturally.

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