4.2) Rsm/Csr regulation by H-NS homologs and IHF
Different NAPs can have similar functions in different species. An example of this is the Csr/Rsm sRNA family, which regulates the CsrA/RsmA proteins and is regulated by either the H-NS family of proteins or IHF, depending on the species (Figure 2 ). Indeed, the central component of the carbon storage regulator (Csr) and the homologous repressor of secondary metabolites (Rsm) systems is an RNA binding protein (CsrA or RsmA) that inhibits protein translation by binding to a stem-loop RNA motif in the 5’-region of its mRNA targets, such as genes involved in metabolism, motility, biofilm formation and quorum sensing and/or pathogenesis. sRNAs such as CsrB/RsmB, CsrC, RsmZ, RsmY and RsmX (the names vary depending on the bacterial species), contain multiple sequence/structural motifs that mimic the RNA motif and sequester the CsrA/RsmA protein. These sRNAs have a redundant titration function, but distinct regulatory pathways. In P. aeruginosa PAO1, the GacS/GacA system transduces regulatory signals to downstream genes by directly controlling the expression of only two genes, rsmY and rsmZ . Castang et al., (2008) showed that MvaT and MvaU, two members of the H-NS family, interact with rsmZ but not with rsmY . The repression of RsmZ transcription by MvaT was validated using mutants defective for the mvaT andmvaU genes, and gene fusions (Brencic et al. , 2009). However, in P. fluorescens, in vitro experiments showed that the AT-rich promoter-linker region of the rsmZ gene has two IHF binding sites, suggesting that IHF is likely to be involved in the regulation of rsmZ rather than the H-NS homologues (Humair, Wackwitz and Haas, 2010). In Salmonella , the sRNAs that sequester CsrA are CsrB and CsrC, which are similar to those in P. fluorescens, as is the regulatory mechanism whereby IHF activates the transcription of csrB but it has no effect on the transcriptional regulation of csrC (Martínez et al. , 2014). Furthermore, in E. amylovora, IHF positively regulates the rsmB sRNA to control motility (Lee and Zhao, 2016). CsrA homologs and Csr/Rsm sRNAs are present in most Gammaproteobacteria species, includingVibrio species and Legionella pneumophila , as well as thePseudomonas species, Salmonella enterica ,Xanthomonas spp. and Erwinia carotovora , suggesting that the regulation illustrated here involving either H-NS homologs or IHF may be widespread in Gammaproteobacteria species, including pathogenic and beneficial biocontrol species.