A tRNA-specific function for tRNA methyltransferase Trm10 is associated with a new tRNA quality control mechanism in Saccharomyces cerevisiae

In Saccharomyces cerevisiae, a single homolog of the tRNA methyltransferase Trm10 performs m(1)G9 modification on 13 different tRNAs. Here we provide evidence that the m(1)G9 modification catalyzed by S. cerevisiae Trm10 plays a biologically important role for one of these tRNA substrates, tRNA(Trp). Overexpression of tRNA(Trp) (and not any of 38 other elongator tRNAs) rescues growth hypersensitivity of the trm10 Delta strain in the presence of the antitumor drug 5-fluorouracil (5FU). Mature tRNA(Trp) is depleted in trm10 Delta cells, and its levels are further decreased upon growth in 5FU, while another Trm10 substrate (tRNA(Gly)) is not affected under these conditions. Thus, m(1)G9 in S. cerevisiae 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 m(1)G9 on mature tRNA(Trp), precursor tRNA(Trp) species accumulate in the same strains, an effect that is due to at least two distinct mechanisms. The levels of mature tRNA(Trp) are rescued in the trm10 Delta met22 Delta strain, consistent with the known role of Met22 in tRNA quality control, where deletion of met22 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(Trp), based on the inability of mutants of each enzyme to rescue the growth of the trm10 Delta strain in the presence of 5FU. Thus, the surveillance of tRNA(Trp) appears to constitute a distinct tRNA quality control pathway in S. cerevisiae.