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

Alexander J. Westermann, Konrad U. Förstner, Fabian Amman, Lars Barquist, Yanjie Chao, Leon N. Schulte, Lydia Müller, Richard Reinhardt, Peter F. Stadler and Jörg Vogel ()
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Alexander J. Westermann: University of Würzburg, RNA Biology Group, Institute for Molecular Infection Biology
Konrad U. Förstner: University of Würzburg, RNA Biology Group, Institute for Molecular Infection Biology
Fabian Amman: University of Leipzig
Lars Barquist: University of Würzburg, RNA Biology Group, Institute for Molecular Infection Biology
Yanjie Chao: University of Würzburg, RNA Biology Group, Institute for Molecular Infection Biology
Leon N. Schulte: University of Würzburg, RNA Biology Group, Institute for Molecular Infection Biology
Lydia Müller: University of Leipzig
Richard Reinhardt: Max Planck Genome Centre Cologne, Max Planck Institute for Plant Breeding Research
Peter F. Stadler: University of Leipzig
Jörg Vogel: University of Würzburg, RNA Biology Group, Institute for Molecular Infection Biology

Nature, 2016, vol. 529, issue 7587, 496-501

Abstract: Abstract 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.

Date: 2016
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DOI: 10.1038/nature16547

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