## 3 Role of Small RNA in Stress Response
### RyhB
OxyS modulates downstream gene expression to mediate DNA damage repair and induce cell cycle arrest, thereby preventing oxidative damage. (**d**) The role of RybB in envelope stress response: RybB is activated by the extracytoplasmic stress sigma factor, \(\sigma^{\text{E}}\) (SigE/RpoE), under envelope stress conditions. It promotes the synthesis of outer membrane proteins to facilitate membrane repair while simultaneously repressing biofilm formation, thereby balancing cellular adaptation to stress. Recent work has identified the role of RyhB in persistor formation [141]. Persistor formation is one of the key strategies employed by bacteria to convert itself into a metabolically inactive state to evade the host immune response (discussed in detail in the antibiotic section). Interestingly, _Salmonella_ contains two copies of _rylhB_ in the genome _ryhB-1_ and _ryhB-2_, which are encoded by separate genes found across all sequenced _Salmonella_ species [139]. These sRNAs share a conserved 33-base region, while the remainder of their sequences exhibit lower conservation. RyhB-1 and RyhB-2 have both overlapping and unique regulatory roles. As in _E. coli_, the expression of both _ryhB-1_ and _ryhB-2_ is repressed by Fur; however, their activation is context-dependent. RyhB-1 is induced by oxidative stress caused by H\({}_{2}\)O\({}_{2}\), whereas RyhB-2 is activated during the stationary growth phase. As in _Salmonella_, sp., [PERSON] et al. characterized two RyhB homologs, RyhB-1 and RyhB-2, in the fish pathogen _Yersinia ruckeri_[142]. Both homologs are induced under iron starvation, repressed by Fur, and stabilized by Hfq, similar to other Enterobacteriaceaeae. However, their functional roles differ. The _\(\Delta\)ryhB-1_ mutant exhibited increased motility, reduced biofilm formation, faster growth, and higher ATP levels, along with enhanced survival in salmon cell cultures. In contrast, the _\(\Delta\)ryhB-2_ mutant was non-motile and formed more biofilm. Gene expression analysis revealed that RyhB-1 and RyhB-2 regulate multiple genes including transcriptional regulators HiL, HiC, HiID, InvF, and RtsA, as well as the regulatory protein RtsB. Additionally, it influences the invasion chaperone SicA, the needle proteins PrgI and InvI, and the effector proteins SipA, SipB, and SipC. Furthermore, RyhB affects the expression of SPI-1-associated genes encoding the effector proteins SopA, SopB, and SopD and tricarboxylic acid (TCA) cycle genes _funA_ and _sdhD_. Interestingly, [PERSON] et al. identified the small RNA IsrR that provides an iron-sparing response in _Staphylococcus_ sp. akin to RyhB [143]. IsrR is repressed by iron, and it downregulates the expression of mRNAs encoding iron-containing enzymes, particularly those involved in anaerobic nitrate respiration. Structural analysis revealed three C-rich regions (CRRs) in IsrR, each contributing differently to target regulation. IsrR is essential for full virulence in a mouse septicemia model, highlighting its role in bacterial survival during infection. Although not orthologous to RyhB or other known sRNAs, IsrR regulates common targets, demonstrating convergent evolution in bacterial iron-sparing responses.