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).