Down-regulation of Porins by a Small RNA Bypasses the Essentiality of the Regulated Intramembrane Proteolysis Protease RseP inEscherichia coli
Journal of Biological Chemistry
Adaptation to extracytoplasmic stress in Escherichia coli depends on the activation of E , normally sequestered by the membrane protein RseA. E is released in response to stress through the successive RseA cleavage by DegS and the RIP protease RseP. E and proteases that free it from RseA are essential. We isolated a multicopy suppressor that alleviated RseP and DegS requirement. The suppressor encodes a novel small RNA, RseX. Its activity required the RNA-binding protein Hfq. We used the
... We used the property that small RNAs are often involved in RNA-RNA interactions to capture RseX putative partners; ompA and ompC mRNA, which encode two major outer membrane proteins, were identified. RseX activity was shown to confer an Hfq-dependent coordinate OmpA and OmpC downregulation. Because RseP is shown to be no longer essential in a strain lacking OmpA and OmpC, we conclude that RseP, which is required for normal E activation, prevents toxicity due to the presence of two specific outer membrane proteins that are down-regulated by RseX. Adaptations to extracytoplasmic stress in Escherichia coli are principally controlled by activation of E , an alternative sigma factor (reviewed in Refs. 1 and 2). E governs expression of genes encoding membrane proteins, proteins involved in phospholipids, lipopolysaccharide and outer membrane biosynthesis, primary metabolism, and signal transduction (3-5). Under nonstress conditions, E is retained at the membrane by the membrane-spanning anti-sigma protein RseA, and is inactive (6, 7). RseA binds to the core RNA polymerase-binding domain of E , thereby inhibiting its assembly with the RNA polymerase (8). Upon extracytoplasmic stress, e.g. induced by ethanol or unfolded proteins (9, 10), RseA undergoes a first cleavage by the DegS protease (11-13). The RseA truncated form is then susceptible to a second protease, RseP (for regulator of E protease, formerly named YaeL), that frees E (13, 14). Further degradation of the RseA cytoplasmic part is performed by the ClpXP protease (15). E , as well as proteases DegS and RseP, which contribute to activation of the E pathway, are essential for bacterial growth (16 -18).