The Kluyveromyces lactis gamma-toxin targets tRNA anticodons.
Kluyveromyces lactis killer strains secrete a heterotrimeric toxin (zymocin), which causes an irreversible growth arrest of sensitive yeast cells. Despite many efforts, the target(s) of the cytotoxic gamma-subunit of zymocin has remained elusive. Here we show that three tRNA species tRNA(Glu)(mcm(5)s(2)UUC), tRNA(Lys)(mcm(5)s(2)UUU), and tRNA(Gln)(mcm(5)s(2)UUG) are the targets of gamma-toxin. The toxin inhibits growth by cleaving these tRNAs at the 3' side of the modified wobble nucleoside 5-methoxycarbonylmethyl-2-thiouridine (mcm(5)s(2)U). Transfer RNA lacking a part of or the entire mcm(5) group is inefficiently cleaved by gamma-toxin, explaining the gamma-toxin resistance of the modification-deficient trm9, elp1-elp6, and kti11-kti13 mutants. The K. lactis gamma-toxin is the first eukaryotic toxin shown to target tRNA.
Lu
Jian
J
Department of Molecular Biology, Umeå University, Sweden.
Huang
Bo
B
Esberg
Anders
A
Johansson
Marcus J O
MJ
Byström
Anders S
AS
D000926:Anticodon / Q000187:drug effects*; D025141:Drug Resistance, Fungal / Q000235:genetics; D015870:Gene Expression; D055646:Killer Factors, Yeast; D007716:Kluyveromyces / Q000737:chemistry*; D009154:Mutation / Q000235:genetics; D009183:Mycotoxins / Q000235:genetics / Q000494:pharmacology*; D009690:Nucleic Acid Conformation; D012343:RNA, Transfer / Q000187:drug effects*; D012441:Saccharomyces cerevisiae / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000502:physiology
D000926:Anticodon; D055646:Killer Factors, Yeast; D009183:Mycotoxins; D029701:Saccharomyces cerevisiae Proteins; C058975:zymocin; D012343:RNA, Transfer