5.1) H-NS is regulated by the sRNA DsrA in E. coli
The regulation of hns by DsrA (downstream of rcsA gene which is positive regulator of the capsular polysaccharide synthesis) was first studied by the group of Susan Gottesman. Their work demonstrated that an overproduction of this small (87 nt) Hfq-dependent RNA activates the initiation of rcsA transcription, thereby counteracting H-NS silencing (Sledjeski and Gottesman, 1995). DsrA was later found to interact with the hns mRNA through specific RNA-RNA base pairing near the translation initiation region (TIR) (Lease, Cusick and Belfort, 1998; Lalaouna et al. , 2015). This interaction promotes mRNA destabilisation by actively recruiting the RNA degradosome complex, which cleaves hns mRNA at 131 nt (Figure 3a ). Furthermore, it reduces protein synthesis as DsrA pairs in the “five-codon window” immediately downstream of the start codon, sterically interfering with the ribosome binding site (TIR) (Lease, Cusick and Belfort, 1998; Lease and Belfort, 2000; Lalaounaet al. , 2015; Lalaouna and Massé, 2016; Wu et al. , 2017). DsrA has the typical structure of a trans- acting RNA, consisting of 3 domains (Sledjeski and Gottesman, 1995; Wu et al. , 2017). The first domain is a single-stranded AU-rich region located between stem-loop I and II that binds to Hfq (Sledjeski, Whitman and Zhang, 2001). The second domain corresponds to the second stem-loop and is involved in the base pairing with hns (Lease, Cusick and Belfort, 1998), and the third domain is a stem-loop that acts as a Rho-independent transcriptional terminator (Figure 3a ). The interaction mechanism between DsrA and hns mRNA has been elucidated by Lalaouna et al., (2015). In summary, Hfq melts out the second stem-loop of DsrA and alters the sRNA conformation, allowing base pairing with the five-codon-window downstream of the start codon in thehns mRNA (Figure 3a ). In response to low temperature or acidic pH stress, the transcription and stability of DsrA is enhanced, thereby modulating the translation of hns mRNAs (Repoila and Gottesman, 2001; Repoila and Darfeuille, 2009; Bak et al. , 2014).