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

In Saccharomyces cerevisiae, a single homolog of the tRNA methyltransferase Trm10 performs m¹G9 modification on 13 different tRNAs. Here we provide evidence that the m¹G9 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 trm10Δ strain in the presence of the antitumor drug 5-fluorouracil (5FU). Mature tRNA^Trp is depleted in trm10Δ cells, and its levels are further decreased upon growth in 5FU, while another Trm10 substrate (tRNA^Gly) is not affected under these conditions. Thus, m¹G9 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 m¹G9 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 trm10Δmet22Δ 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 trm10Δ strain in the presence of 5FU. Thus, the surveillance of tRNA^Trp appears to constitute a distinct tRNA quality control pathway in S. cerevisiae.