Synthesis of the regulatory RNA CsrC in Yersinia pseudotuberculosis is mediated by the RNA-binding protein CsrA, the nucleoid-associated proteins YmoA, H-NS and the RNA-chaperon Hfq

Regulatory RNAs are important tools for virulence factor expression in the enteric pathogen Yersinia pseudotuberculosis, which colonizes the human host by passing the M-cells in the small intestine to reach deeper tissues. To efficiently adhere to and invade into the M-cells, the bacteria produce the outer membrane protein invasin. In vitro, invasin is expressed at lower temperatures, in complex medium and during stationary growth in presence of the global regulator RovA. rovA transcription is regulated by the Carbon storage regulator (Csr) system. This system comprises the RNA-binding protein CsrA and two regulatory RNAs, CsrC and CsrB. CsrA indirectly represses rovA expression in minimal medium. This is counteracted by the presence of CsrC or CsrB. CsrC is synthesized under invasin-inducing conditions, via a sophisticated interplay between CsrA, the nucleoid-associated proteins YmoA and H-NS and the RNA-chaperon Hfq. CsrC is stabilized by CsrA and YmoA. CsrA inhibits CsrC degradation by binding to the RNA, whereas YmoA indirectly supports CsrC. In microarrays, the absence of ymoA leads to higher expression of RNases and related factors which might facilitate the CsrC turnover. The global repressor H-NS activates CsrC synthesis in a posttranscriptional manner showing RNA-binding ability. Further, we analyzed that Hfq does not influence the CsrC stability but that of CsrB. Instead, an hfq deletion reduces csrC gene expression. All this ensures the presence of CsrC and thus formation of invasin in the beginning of the infection.