Rapid tRNA Decay Can Result from Lack of Nonessential Modifications

SummaryThe biological role of many nonessential tRNA modifications outside of the anticodon remains elusive despite their evolutionary conservation. We show here that m7G46 methyltransferase Trm8p/Trm82p acts as a hub of synthetic interactions with several tRNA modification enzymes, resulting in temperature-sensitive growth. Analysis of three double mutants indicates reduced levels of tRNAVal(AAC), consistent with a role of the corresponding modifications in maintenance of tRNA levels. Detailed examination of a trm8-Δ trm4-Δ double mutant demonstrates rapid degradation of preexisting tRNAVal(AAC) accompanied by its de-aminoacylation. Multiple copies of tRNAVal(AAC) suppress the trm8-Δ trm4-Δ growth defect, directly implicating this tRNA in the phenotype. These results define a rapid tRNA degradation (RTD) pathway that is independent of the TRF4/RRP6-dependent nuclear surveillance pathway. The degradation of an endogenous tRNA species at a rate typical of mRNA decay demonstrates a critical role of nonessential modifications for tRNA stability and cell survival.