The Kluyveromyces lactis gamma-toxin targets tRNA anticodons.
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Journal: 2005/December - RNA
ISSN: 1355-8382
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 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.
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RNA 11(11): 1648-1654
PMID: 16244131

The <em>Kluyveromyces lactis</em> γ-toxin targets tRNA anticodons

Department of Molecular Biology, Umeå University, 901 87 Umeå, Sweden
Reprint requests to: Anders S. Byström, Department of Molecular Biology, Umeå University, 901 87 Umeå, Sweden; e-mail: es.umu.loiblom@mortsyB.srednA; fax 46-90-77-26-30.
Reprint requests to: Anders S. Byström, Department of Molecular Biology, Umeå University, 901 87 Umeå, Sweden; e-mail: es.umu.loiblom@mortsyB.srednA; fax 46-90-77-26-30.
Received 2005 Jul 25; Accepted 2005 Aug 22.
Copyright © Copyright 2005 by RNA Society

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 tRNAmcmsUUC, tRNAmcmsUUU, and tRNAmcmsUUG 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 (mcmsU). Transfer RNA lacking a part of or the entire mcm 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
Abstract

Acknowledgments

We thank Drs. L. Symington and K. Arndt for S. cerevisiae strains W303-1A, W303-1B, and CY4029. Dr. N. Gunge is acknowledged for K. lactis strain 2105-1D. Drs. G.R. Björk, H. Wolf-Watz, and S. Tuck are acknowledged for valuable discussions. This work was financially supported by the Swedish Research Council (621-2004-2563) and the Swedish Cancer Society (3516-B03-10XAB). M.J.O.J. was supported by grants from the Swedish Research Council (621-2004-1700) and the Swedish Cancer Society (0608-B04-33XAB).

Acknowledgments

Notes

Article and publication are at http://www.rnajournal.org/cgi/doi/10.1261/rna.2172105.

Notes
Article and publication are at http://www.rnajournal.org/cgi/doi/10.1261/rna.2172105.

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