Rapid tRNA Decay Can Result from Lack of Nonessential Modifications

Molecular Cell, Volume 21, Issue 1, 6 January 2006, Pages 87-96
Andrei Alexandrov, Irina Chernyakov, Weifeng Gu, Shawna L. Hiley, Timothy R. Hughes, Elizabeth J. Grayhack and Eric M. Phizicky

Summary

The biological role of many nonessential tRNA modifications outside of the anticodon remains elusive despite their evolutionary conservation. We show here that mG 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 tRNA, consistent with a role of the corresponding modifications in maintenance of tRNA levels. Detailed examination of a double mutant demonstrates rapid degradation of preexisting tRNA accompanied by its de-aminoacylation. Multiple copies of tRNA suppress the growth defect, directly implicating this tRNA in the phenotype. These results define a rapid tRNA degradation (RTD) pathway that is independent of the /-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.