RalR (a DNase) and RalA (a small RNA) form a type I toxin-antitoxin system in Escherichia coli

Nucleic Acids Res. 2014 Jun;42(10):6448-62. doi: 10.1093/nar/gku279. Epub 2014 Apr 19.


For toxin/antitoxin (TA) systems, no toxin has been identified that functions by cleaving DNA. Here, we demonstrate that RalR and RalA of the cryptic prophage rac form a type I TA pair in which the antitoxin RNA is a trans-encoded small RNA with 16 nucleotides of complementarity to the toxin mRNA. We suggest the newly discovered antitoxin gene be named ralA for RalR antitoxin. Toxin RalR functions as a non-specific endonuclease that cleaves methylated and unmethylated DNA. The RNA chaperone Hfq is required for RalA antitoxin activity and appears to stabilize RalA. Also, RalR/RalA is beneficial to the Escherichia coli host for responding to the antibiotic fosfomycin. Hence, our results indicate that cryptic prophage genes can be functionally divergent from their active phage counterparts after integration into the host genome.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Bacterial Toxins / biosynthesis
  • Bacterial Toxins / genetics
  • Bacterial Toxins / metabolism*
  • Base Pairing
  • Drug Resistance, Bacterial
  • Endodeoxyribonucleases / biosynthesis
  • Endodeoxyribonucleases / genetics
  • Endodeoxyribonucleases / metabolism*
  • Escherichia coli / drug effects
  • Escherichia coli / enzymology*
  • Escherichia coli / genetics*
  • Escherichia coli Proteins / biosynthesis
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / metabolism*
  • Escherichia coli Proteins / physiology
  • Fosfomycin / pharmacology
  • Host Factor 1 Protein / physiology
  • Protein Biosynthesis
  • RNA, Messenger / chemistry
  • RNA, Small Untranslated / chemistry
  • RNA, Small Untranslated / genetics
  • RNA, Small Untranslated / metabolism*
  • Transcription Factors / biosynthesis
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*


  • Anti-Bacterial Agents
  • Bacterial Toxins
  • Escherichia coli Proteins
  • Hfq protein, E coli
  • Host Factor 1 Protein
  • RNA, Messenger
  • RNA, Small Untranslated
  • RalR protein, E coli
  • Transcription Factors
  • Fosfomycin
  • Endodeoxyribonucleases