Discovering RNA-Based Regulatory Systems for Yersinia Virulence

Abstract

The genus Yersinia includes three human pathogenic species, Yersinia pestis, the causative agent of the bubonic and pneumonic plague, and enteric pathogens Y. enterocolitica and Y. pseudotuberculosis that cause a number of gut-associated diseases. Over the past years a large repertoire of RNA-based regulatory systems has been discovered in these pathogens using different RNA-seq based approaches. Among them are several conserved or species-specific RNA-binding proteins, regulatory and sensory RNAs as well as various RNA-degrading enzymes. Many of them were shown to control the expression of important virulence-relevant factors and have a very strong impact on Yersinia virulence. The precise targets, the molecular mechanism and their role for Yersinia pathogenicity is only known for a small subset of identified genus- or species-specific RNA-based control elements. However, the ongoing development of new RNA-seq based methods and data analysis methods to investigate the synthesis, composition, translation, decay, and modification of RNAs in the bacterial cell will help us to generate a more comprehensive view of Yersinia RNA biology in the near future.

Keywords: Csr/Rsm system; RNA processing; RNA stability; RNA thermometer; gene regulation; small regulatory RNAs; virulence.

Figure 1

Available RNA-seq derived techniques, which can be used to study RNA-based control mechanisms in Yersinia. Different RNA-seq based techniques allow rapid and global investigation of transcript expression, transcription start sites, promoter structures, 5′- and 3′-UTR properties (dRNA-Seq), as well as binding of RNA-binding proteins to RNAs, such as CsrA, Hfq, and YopD (RIP-seq, CLIP-seq), RNA-RNA interactions facilitated by protein interaction (RIL-Seq), translation (Ribo-seq), and RNA processing and decay by heat-sensitive RNase E (rne^TS) (TIER-seq).

Figure 2

Different RNA-based regulatory mechanisms that control virulence in Yersinia. Global RNA biology approaches have been used to identify sRNAs, asRNAs, and sensory RNAs (RNA thermometer and riboswitches) as well as important RNA-binding proteins implicated in Yersinia virulence control.