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Nucleic Acids Res. 2016 Feb 18;44(3):1256-70. doi: 10.1093/nar/gkv1370. Epub 2016 Jan 5.

tRNA is a new target for cleavage by a MazF toxin.

Author information

1
Department of Biochemistry and Molecular Biology, Rutgers University, Robert Wood Johnson Medical School, Piscataway, NJ, USA.
2
Waksman Institute, Rutgers University, Piscataway, NJ, USA Department of Genetics, Rutgers University, Piscataway, NJ, USA.
3
Division of Infectious Diseases, Boston Children's Hospital/Harvard Medical School, Boston, MA, USA.
4
Department of Computer Science, University of Massachusetts Boston, Boston, MA, USA.
5
Waksman Institute, Rutgers University, Piscataway, NJ, USA Department of Genetics, Rutgers University, Piscataway, NJ, USA Member, Rutgers Cancer Institute of New Jersey, NJ, USA.
6
Department of Biochemistry and Molecular Biology, Rutgers University, Robert Wood Johnson Medical School, Piscataway, NJ, USA Member, Rutgers Cancer Institute of New Jersey, NJ, USA nancy.woychik@rutgers.edu.

Abstract

Toxin-antitoxin (TA) systems play key roles in bacterial persistence, biofilm formation and stress responses. The MazF toxin from the Escherichia coli mazEF TA system is a sequence- and single-strand-specific endoribonuclease, and many studies have led to the proposal that MazF family members exclusively target mRNA. However, recent data indicate some MazF toxins can cleave specific sites within rRNA in concert with mRNA. In this report, we identified the repertoire of RNAs cleaved by Mycobacterium tuberculosis toxin MazF-mt9 using an RNA-seq-based approach. This analysis revealed that two tRNAs were the principal targets of MazF-mt9, and each was cleaved at a single site in either the tRNA(Pro14) D-loop or within the tRNA(Lys43) anticodon. This highly selective target discrimination occurs through recognition of not only sequence but also structural determinants. Thus, MazF-mt9 represents the only MazF family member known to target tRNA and to require RNA structure for recognition and cleavage. Interestingly, the tRNase activity of MazF-mt9 mirrors basic features of eukaryotic tRNases that also generate stable tRNA-derived fragments that can inhibit translation in response to stress. Our data also suggest a role for tRNA distinct from its canonical adapter function in translation, as cleavage of tRNAs by MazF-mt9 downregulates bacterial growth.

PMID:
26740583
PMCID:
PMC4756823
DOI:
10.1093/nar/gkv1370
[Indexed for MEDLINE]
Free PMC Article

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