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Journal of Bacteriology, February 2009, p. 1191-1199, Vol. 191, No. 4
0021-9193/09/$08.00+0     doi:10.1128/JB.01013-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

HicA of Escherichia coli Defines a Novel Family of Translation-Independent mRNA Interferases in Bacteria and Archaea ^,

Mikkel G. Jørgensen,^1,3 Deo P. Pandey,² Milena Jaskolska,³ and Kenn Gerdes^1*

Centre for Bacterial Cell Biology, Institute for Cell and Molecular Biosciences, Medical School, Newcastle University, Newcastle NE2 4HH, United Kingdom,¹ Department of Cell Biology, Sciences III, University of Genève 30, quai Ernest-Ansermet, 1211 Geneva 4, Switzerland,² Department of Biochemistry and Molecular Biology, University of Southern Denmark, DK-5230 Odense M, Denmark³

Received 23 July 2008/ Accepted 30 November 2008

Toxin-antitoxin (TA) loci are common in free-living bacteria and archaea. TA loci encode a stable toxin that is neutralized by a metabolically unstable antitoxin. The antitoxin can be either a protein or an antisense RNA. So far, six different TA gene families, in which the antitoxins are proteins, have been identified. Recently, Makarova et al. (K. S. Makarova, N. V. Grishin, and E. V. Koonin, Bioinformatics 22:2581-2584, 2006) suggested that the hicAB loci constitute a novel TA gene family. Using the hicAB locus of Escherichia coli K-12 as a model system, we present evidence that supports this inference: expression of the small HicA protein (58 amino acids [aa]) induced cleavage in three model mRNAs and tmRNA. Concomitantly, the global rate of translation was severely reduced. Using tmRNA as a substrate, we show that HicA-induced cleavage does not require the target RNA to be translated. Expression of HicB (145 aa) prevented HicA-mediated inhibition of cell growth. These results suggest that HicB neutralizes HicA and therefore functions as an antitoxin. As with other antitoxins (RelB and MazF), HicB could resuscitate cells inhibited by HicA, indicating that ectopic production of HicA induces a bacteriostatic rather than a bactericidal condition. Nutrient starvation induced strong hicAB transcription that depended on Lon protease. Mining of 218 prokaryotic genomes revealed that hicAB loci are abundant in bacteria and archaea.

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* Corresponding author. Mailing address: Institute for Cell and Molecular Biosciences, Medical School, Newcastle University, Newcastle NE2 4HH, United Kingdom. Phone: 44 0191 222 5318. Fax: 44 0191 222 2467. E-mail: kenn.gerdes{at}ncl.ac.uk

Published ahead of print on 5 December 2008.

Supplemental material for this article may be found at http://jb.asm.org/.

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Journal of Bacteriology, February 2009, p. 1191-1199, Vol. 191, No. 4
0021-9193/09/$08.00+0     doi:10.1128/JB.01013-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

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