A TRNA-specific Function for TRNA Methyltransferase Trm10 is Associated with a New TRNA Quality Control Mechanism in

In , a single homolog of the tRNA methyltransferase Trm10 performs mG9 modification on 13 different tRNAs. Here we provide evidence that the mG9 modification catalyzed by Trm10 plays a biologically important role for one of these tRNA substrates, tRNA Overexpression of tRNA (and not any of 38 other elongator tRNAs) rescues growth hypersensitivity of the strain in the presence of the antitumor drug 5-fluorouracil (5FU). Mature tRNA is depleted in cells, and its levels are further decreased upon growth in 5FU, while another Trm10 substrate (tRNA) is not affected under these conditions. Thus, mG9 in is another example of a tRNA modification that is present on multiple tRNAs but is only essential for the biological function of one of those species. In addition to the effects of mG9 on mature tRNA, precursor tRNA species accumulate in the same strains, an effect that is due to at least two distinct mechanisms. The levels of mature tRNA are rescued in the strain, consistent with the known role of Met22 in tRNA quality control, where deletion of causes inhibition of 5'-3' exonucleases that catalyze tRNA decay. However, none of the known Met22-associated exonucleases appear to be responsible for the decay of hypomodified tRNA, based on the inability of mutants of each enzyme to rescue the growth of the strain in the presence of 5FU. Thus, the surveillance of tRNA appears to constitute a distinct tRNA quality control pathway in .