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Proc Natl Acad Sci U S A. 2015 Aug 25;112(34):E4772-81. doi: 10.1073/pnas.1507825112. Epub 2015 Aug 11.

Small RNA-based feedforward loop with AND-gate logic regulates extrachromosomal DNA transfer in Salmonella.

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Department of Molecular Biology, Princeton University, Princeton, NJ 08544; Institute for Molecular Infection Biology, University of Würzburg, 97080 Wurzburg, Germany; Department of Biology I, Ludwig-Maximilians-University Munich, 82152 Martinsried, Germany;
Departamento de Genética, Facultad de Biología, Universidad de Sevilla, 41080 Seville, Spain.
Institute for Molecular Infection Biology, University of Würzburg, 97080 Wurzburg, Germany;


Horizontal gene transfer via plasmid conjugation is a major driving force in microbial evolution but constitutes a complex process that requires synchronization with the physiological state of the host bacteria. Although several host transcription factors are known to regulate plasmid-borne transfer genes, RNA-based regulatory circuits for host-plasmid communication remain unknown. We describe a posttranscriptional mechanism whereby the Hfq-dependent small RNA, RprA, inhibits transfer of pSLT, the virulence plasmid of Salmonella enterica. RprA employs two separate seed-pairing domains to activate the mRNAs of both the sigma-factor σ(S) and the RicI protein, a previously uncharacterized membrane protein here shown to inhibit conjugation. Transcription of ricI requires σ(S) and, together, RprA and σ(S) orchestrate a coherent feedforward loop with AND-gate logic to tightly control the activation of RicI synthesis. RicI interacts with the conjugation apparatus protein TraV and limits plasmid transfer under membrane-damaging conditions. To our knowledge, this study reports the first small RNA-controlled feedforward loop relying on posttranscriptional activation of two independent targets and an unexpected role of the conserved RprA small RNA in controlling extrachromosomal DNA transfer.


Hfq; RprA; feedforward control; plasmid conjugation; sRNA

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