Dual RNA-seq Unveils Noncoding RNA Functions in Host-Pathogen Interactions

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Proteins / metabolism
  • Female
  • Gene Expression Regulation / genetics*
  • Genes, Bacterial / genetics
  • HeLa Cells
  • Host-Pathogen Interactions / genetics*
  • Humans
  • Janus Kinases / metabolism
  • Mice
  • Microbial Viability / genetics
  • RNA, Bacterial / genetics*
  • RNA, Bacterial / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Untranslated / genetics*
  • RNA, Untranslated / metabolism
  • STAT Transcription Factors / metabolism
  • Salmonella typhimurium / cytology
  • Salmonella typhimurium / genetics*
  • Salmonella typhimurium / pathogenicity
  • Signal Transduction / genetics
  • Transcriptome / genetics
  • Virulence / genetics

Substances

  • Bacterial Proteins
  • RNA, Bacterial
  • RNA, Messenger
  • RNA, Untranslated
  • STAT Transcription Factors
  • PhoP protein, Bacteria
  • Janus Kinases

Associated data

  • GEO/GSE60144