Rapid tRNA decay can result from lack of nonessential modifications.
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.
Alexandrov
Andrei
A
Department of Biochemistry and Biophysics, University of Rochester School of Medicine, Rochester, New York 14642, USA.
Chernyakov
Irina
I
Gu
Weifeng
W
Hiley
Shawna L
SL
Hughes
Timothy R
TR
Grayhack
Elizabeth J
EJ
Phizicky
Eric M
EM
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*
D000926:Anticodon; D012366:RNA, Transfer, Val; D029701:Saccharomyces cerevisiae Proteins; D012359:tRNA Methyltransferases; C036814:tRNA (guanine-N7-)-methyltransferase