Conserved small non-coding RNAs that belong to the sigmaE regulon: role in down-regulation of outer membrane proteins

Enteric bacteria respond to misfolded proteins by activating the transcription of "heat shock" genes. These genes are arranged in two major regulons controlled by the alternative sigma factors sigmaH and sigmaE. The two transcription factors coordinate the stress response in different cellular compartments; the sigmaH regulon is induced by stress in the cytoplasm whereas the sigmaE regulon is activated by stress signals in the cell envelope. In Escherichia coli sigmaE plays a central role in maintaining cell envelope integrity both under stress conditions and during normal growth. Previous work established that sigmaE is essential for viability of the bacterium and up-regulates expression of approximately 100 protein-encoding genes that influences nearly every aspect of the cell envelope. Moreover, the expression of several outer membrane proteins is down-regulated upon sigmaE activation. Here, we show that two Hfq-binding small RNAs, MicA and RybB, are under positive control of sigmaE. Transient induction of RybB resulted in decreased levels of the mRNAs encoding OmpC and OmpW. sigmaE -mediated regulation of ompC and ompW expression was abolished in strains lacking RybB or Hfq. Recently MicA was shown to act in destabilizing the ompA transcript when rapidly grown cells entered the stationary phase of growth. Also, the alternative sigma factor down-regulates this message in a small non-coding RNA-dependent fashion. These findings add the sigmaE regulon to the growing list of stress induced regulatory circuits that include small regulatory RNAs and provide insight in a homeostatic loop that prevent a build-up of unassembled outer membrane proteins in the envelope.