SigmaE

SigmaE, also known as sigma factor E or RpoE, is an extracytoplasmic function (ECF) sigma factor of bacterial RNA polymerase that directs transcription in response to envelope and periplasmic stress, particularly in Gram-negative bacteria such as Escherichia coli. It regulates a group of genes that help restore cell envelope integrity and protein folding in the periplasm.

Under normal conditions, sigmaE is kept inactive by its anti-sigma factor RseA, an inner membrane protein. When envelope stress occurs—such as accumulation of misfolded outer membrane proteins—the periplasmic protease DegS detects these cues and initiates a proteolytic cascade that cleaves RseA. Subsequent intramembrane proteolysis by RseP (YaeL) releases sigmaE from the membrane, allowing it to bind RNA polymerase and activate transcription of its regulon. RseB and other factors modulate this signaling, and feedback mechanisms exist to restore repression when stress subsides.

The sigmaE regulon includes periplasmic chaperones and proteases (for example, DegP/HtrA, FkpA, Skp), components involved in lipopolysaccharide assembly, and other proteins that maintain outer membrane integrity and protein folding quality control. This response is part of a coordinated network with other stress pathways, such as Cpx and heat shock responses, to promote survival during envelope disruption.

SigmaE is essential for managing extracytoplasmic stress in many bacteria and contributes to pathogenicity in some species. Its activity is a benchmark example of regulated intramembrane proteolysis guiding transcriptional programs in bacterial stress responses.