tRNAGlu wobble uridine methylation by Trm9 identifies Elongator's key role for zymocin-induced cell death in yeast.
Zymocin-induced cell death in Saccharomyces cerevisiae requires the toxin-target (TOT) effector Elongator, a protein complex with functions in transcription, exocytosis and tRNA modification. In line with the latter, trm9Delta cells lacking a tRNA methylase specific for wobble uridine (U(34)) residues survive zymocin and in excess, the Trm9 substrate tRNA(Glu) copies zymocin protection of Elongator mutants. Phenotypes typical of a tot3/elp3Delta Elongator mutant are absent from trm9Delta cells but copied in a tot3Deltatrm9Delta double mutant suggesting that Elongator acts upstream of Trm9. Consistent with Elongator-dependent tRNA modification being more important to mRNA decoding than Trm9, SUP4 and SOE1TRNA suppressors are highly sensitive to loss of Elongator and tRNA U(34) hypomodification. As Trm9 overexpression counteracts the effect of high-copy tRNA(Glu), zymocin suppression by high-copy tRNA(Glu) may reflect tRNA hypomethylation of trm9Delta cells. Thus, Trm9 methylation may enable recognition of tRNA by zymocin, a notion supported by a dramatic reduction of tRNA(Glu) levels in zymocin-treated cells and by cytotoxic zymocin residues conserved between bacterial nucleases and a tRNA modifying GTPase. In sum, Trm9 is a bona fideTOT pathway component whose methylation may be hijacked by zymocin to target tRNA function and eventually, mRNA translation.
Jablonowski
Daniel
D
Biologicum, Institut für Genetik, Martin-Luther-Universität Halle-Wittenberg, Weinbergweg 10, D-06120 Halle, Saale, Germany.
Zink
Sabrina
S
Mehlgarten
Constance
C
Daum
Gabriele
G
Schaffrath
Raffael
R
D001483:Base Sequence; D016923:Cell Death / Q000187:drug effects*; D017931:DNA Primers; D004843:Epistasis, Genetic; D055646:Killer Factors, Yeast; D008745:Methylation; D009183:Mycotoxins / Q000494:pharmacology*; D012352:RNA, Transfer, Glu / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000187:drug effects*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D014529:Uridine / Q000378:metabolism*; D012359:tRNA Methyltransferases / Q000378:metabolism*
D017931:DNA Primers; D055646:Killer Factors, Yeast; D009183:Mycotoxins; D012352:RNA, Transfer, Glu; D029701:Saccharomyces cerevisiae Proteins; C058975:zymocin; C480488:TRM9 protein, S cerevisiae; D012359:tRNA Methyltransferases; D014529:Uridine