Messenger RNA interferase RelE controls relBE transcription by conditional cooperativity

Authors

  • Martin Overgaard,

    1. Department of Biochemistry and Molecular Biology, University of Southern Denmark, Campusvej 55, DK-5230 Odense M, Denmark.
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  • Jonas Borch,

    1. Department of Biochemistry and Molecular Biology, University of Southern Denmark, Campusvej 55, DK-5230 Odense M, Denmark.
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  • Mikkel G. Jørgensen,

    1. Department of Biochemistry and Molecular Biology, University of Southern Denmark, Campusvej 55, DK-5230 Odense M, Denmark.
    2. Institute for Cell and Molecular Biosciences, Medical School, Newcastle University, Newcastle NE2 4HH, UK.
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  • Kenn Gerdes

    Corresponding author
    1. Institute for Cell and Molecular Biosciences, Medical School, Newcastle University, Newcastle NE2 4HH, UK.
      *E-mail kenn.gerdes@ncl.ac.uk; Tel. (+44) 191 2225318; Fax (+44) 191 2227424.
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*E-mail kenn.gerdes@ncl.ac.uk; Tel. (+44) 191 2225318; Fax (+44) 191 2227424.

Summary

Prokaryotic toxin–antitoxin (TA) loci consist of two genes in an operon that encodes a metabolically stable toxin and an unstable antitoxin. The antitoxin neutralizes its cognate toxin by forming a tight complex with it. In all cases known, the antitoxin autoregulates TA operon transcription by binding to one or more operators in the promoter region while the toxin functions as a co-repressor of transcription. Interestingly, the toxin can also stimulate TA operon transcription. Here we analyse mechanistic aspects of how RelE of Escherichia coli can function both as a co-repressor and as a derepressor of relBE transcription. When RelB was in excess to RelE, two trimeric RelB2•RelE complexes bound cooperatively to two adjacent operator sites in the relBE promoter region and repressed transcription. In contrast, RelE in excess stimulated relBE transcription and released the RelB2•RelE complex from operator DNA. A mutational analysis of the operator sites showed that RelE in excess counteracted cooperative binding of the RelB2•RelE complexes to the operator sites. Thus, RelE controls relBE transcription by conditional cooperativity.

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