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

Abstract

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, tRNATrp. Overexpression of tRNATrp (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 tRNATrp is depleted in trm10Δ cells, and its levels are further decreased upon growth in 5FU, while another Trm10 substrate (tRNAGly) 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 tRNATrp, precursor tRNATrp species accumulate in the same strains, an effect that is due to at least two distinct mechanisms. The levels of mature tRNATrp 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 decay of hypomodified tRNATrp, based on inability of mutants of each enzyme to rescue growth of the trm10Δ strain in the presence of 5FU. Thus, the surveillance of tRNATrp appears to constitute a distinct tRNA quality control pathway in S. cerevisiae.

Beyond the Anticodon: tRNA Core Modifications and Their Impact on Structure, Translation and Stress Adaptation

“…Recently, a study reported a new tRNA quality control mechanism in S. cerevisiae , in which mature lacking m 1 G9 is eliminated by a Met22-dependent but RTD- and nuclear surveillance-independent degradation pathway ( Table 1 ) [ 93 ]. Further investigation is definitely needed to identify the nucleases responsible for this degradation and the molecular mechanisms of this intriguing tRNA quality control pathway.…”

“…Further investigation is definitely needed to identify the nucleases responsible for this degradation and the molecular mechanisms of this intriguing tRNA quality control pathway. Interestingly, m 1 G9 prevents the degradation of , whereas its absence in has no effect on its cellular stability [ 93 ], adding to the list of known examples of tRNA core modifications that have different effects depending on the tRNA species and are only required for the cellular stability of a particular tRNA [ 72 ].…”