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Nature. 2016 Jan 28;529(7587):496-501. doi: 10.1038/nature16547. Epub 2016 Jan 20.

Dual RNA-seq unveils noncoding RNA functions in host-pathogen interactions.

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University of Würzburg, RNA Biology Group, Institute for Molecular Infection Biology, Josef-Schneider-Straße 2/D15, D-97080 Würzburg, Germany.
University of Würzburg, Core Unit Systems Medicine, Josef-Schneider-Straße 2/D15, D-97080 Würzburg, Germany.
University of Leipzig, Department of Computer Science and Interdisciplinary Center for Bioinformatics, Härtelstraße 16-18, D-04107 Leipzig, Germany.
University of Vienna, Theoretical Biochemistry Group, Institute for Theoretical Chemistry, Währinger Straße 17, A-1090 Vienna, Austria.
Max Planck Genome Centre Cologne, Max Planck Institute for Plant Breeding Research, Carl-von-Linné-Weg 10, D-50829 Cologne, Germany.
Max Planck Institute for Mathematics in the Sciences, Inselstraße 22, D-04103 Leipzig, Germany.
Santa Fe Institute, 1399 Hyde Park Rd, Santa Fe, New Mexico 87501, USA.
Research Centre for Infectious Diseases (ZINF), University of Würzburg, D-97070 Würzburg, Germany.


Bacteria express many small RNAs for which the regulatory roles in pathogenesis have remained poorly understood due to a paucity of robust phenotypes in standard virulence assays. Here we use a generic 'dual RNA-seq' approach to profile RNA expression simultaneously in pathogen and host during Salmonella enterica serovar Typhimurium infection and reveal the molecular impact of bacterial riboregulators. We identify a PhoP-activated small RNA, PinT, which upon bacterial internalization temporally controls the expression of both invasion-associated effectors and virulence genes required for intracellular survival. This riboregulatory activity causes pervasive changes in coding and noncoding transcripts of the host. Interspecies correlation analysis links PinT to host cell JAK-STAT signalling, and we identify infection-specific alterations in multiple long noncoding RNAs. Our study provides a paradigm for a sensitive RNA-based analysis of intracellular bacterial pathogens and their hosts without physical separation, as well as a new discovery route for hidden functions of pathogen genes.

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