title: Rapid tRNA decay can result from lack of nonessential modifications.
abstract: The 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 tRNA(Val(AAC)), consistent with a role of the corresponding modifications in maintenance of tRNA levels. Detailed examination of a trm8-delta trm4-delta double mutant demonstrates rapid degradation of preexisting tRNA(Val(AAC)) accompanied by its de-aminoacylation. Multiple copies of tRNA(Val(AAC)) suppress the trm8-delta trm4-delta 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.
authors.affiliation: Department of Biochemistry and Biophysics, University of Rochester School of Medicine, Rochester, New York 14642, USA.
authors.forename: Andrei
authors.initials: A
authors.lastname: Alexandrov
authors.forename: Irina
authors.initials: I
authors.lastname: Chernyakov
authors.forename: Weifeng
authors.initials: W
authors.lastname: Gu
authors.forename: Shawna L
authors.initials: SL
authors.lastname: Hiley
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Hughes
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Grayhack
authors.forename: Eric M
authors.initials: EM
authors.lastname: Phizicky
mesh_terms: D000926:Anticodon; D017353:Gene Deletion; D006801:Humans; D009690:Nucleic Acid Conformation; D020411:Oligonucleotide Array Sequence Analysis; D012323:RNA Processing, Post-Transcriptional; D020871:RNA Stability; D012366:RNA, Transfer, Val / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D013696:Temperature; D046249:Transfer RNA Aminoacylation; D012359:tRNA Methyltransferases / Q000235:genetics / Q000378:metabolism*
chemical_list: D000926:Anticodon; D012366:RNA, Transfer, Val; D029701:Saccharomyces cerevisiae Proteins; D012359:tRNA Methyltransferases; C036814:tRNA (guanine-N7-)-methyltransferase