Tartu study links protein-making errors to faster mutations

Errors in protein production may accelerate genetic mutations under certain conditions, a University of Tartu doctoral study has found, ERR reported. Researchers found that cells lacking the TruA enzyme accumulated mutations five times faster.

Ribosomes make proteins by reading instructions carried from DNA by messenger RNA, or mRNA. About once in every few thousand codons, a ribosome may shift the mRNA reading frame or insert the wrong amino acid. If an error affects a critically important protein, that protein may no longer function properly, potentially contributing to mutations in DNA.

Doctoral researcher Karl Jürgenstein investigated whether the link between protein-production accuracy and genome stability, previously studied mainly in the bacterium Escherichia coli, also applied to other bacteria. He focused on Pseudomonas, a bacterial genus whose members are found in soil and in the human body.

Jürgenstein reduced the accuracy of translation, the process by which cells make proteins from mRNA instructions, in two ways. He removed the TruA and RluA enzymes, which are needed for the normal functioning of tRNA molecules that reduce protein synthesis, and altered the ribosomal protein uS5, which helps the ribosome distinguish between correct and incorrect codons.

Without TruA, overall protein-production accuracy fell and cells accumulated mutations five times faster. Mutation frequency also rose in most uS5 mutants with reduced protein-production accuracy.

The findings indicate that the relationship between protein-synthesis errors and lasting changes in the genome depends on the conditions and the specific genetic changes involved.