HicA of Escherichia coli defines a novel family of translation-independent mRNA interferases in bacteria and archaea

Mikkel G Jørgensen, Deo P Pandey, Milena Jaskolska, Kenn Gerdes

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

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.
Original languageEnglish
JournalJournal of Bacteriology
Volume191
Issue number4
Pages (from-to)1191-9
Number of pages8
ISSN0021-9193
DOIs
Publication statusPublished - 1. Feb 2009

Keywords

  • Archaea
  • Escherichia coli
  • Escherichia coli Proteins
  • Gene Expression Regulation, Bacterial
  • Multigene Family
  • Protein Biosynthesis
  • RNA, Messenger

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