The Kluyveromyces lactis γ-toxin targets tRNA anticodons

Abstract

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 γ-subunit of zymocin has remained elusive. Here we show that three tRNA species tRNA^Glu_mcm⁵s²UUC, tRNA^Lys_mcm⁵s²UUU, and tRNA^Gln_mcm⁵s²UUG are the targets of γ-toxin. The toxin inhibits growth by cleaving these tRNAs at the 3′ side of the modified wobble nucleoside 5-methoxycarbonylmethyl-2-thiouridine (mcm⁵s²U). Transfer RNA lacking a part of or the entire mcm⁵ group is inefficiently cleaved by γ-toxin, explaining the γ-toxin resistance of the modification-deficient trm9, elp1-elp6, and kti11-kti13 mutants. The K. lactis γ-toxin is the first eukaryotic toxin shown to target tRNA.

Keywords

• K. lactis γ-toxin
• tRNA endonuclease
• ELP3
• TRM9
• 5-methoxycarbonylmethyl-2-thiouridine