Modulating RssB activity: IraP, a novel regulator of sigma(S) stability in Escherichia coli.

The sigma(S) subunit of Escherichia coli RNA polymerase regulates the expression of stationary phase and stress response genes. sigma(S) is highly unstable in exponentially growing cells, whereas its stability increases dramatically upon starvation or under certain stress conditions. The degradation of sigma(S) is controlled by the phosphorylatable adaptor protein RssB and the ClpXP protease. RssB specifically directs sigma(S) to ClpXP. An unanswered question is how RssB-mediated degradation of sigma(S) is blocked by conditions such as glucose or phosphate starvation. We report here the identification and characterization of a new regulator of sigma(S) stability, IraP (inhibitor of RssB activity during phosphate starvation), that stabilizes sigma(S) both in vivo and in vitro. Deletion of iraP interferes with sigma(S) stabilization during phosphate starvation, but not during carbon starvation, and has a partial effect in stationary phase and nitrogen starvation. IraP interferes with RssB-dependent degradation of sigma(S) through a direct protein-protein interaction with RssB. A point mutant of IraP was isolated and found to be defective both for inhibition of sigma(S) degradation and interaction with RssB. Our results reveal a novel mechanism of regulation of sigma(S) stability through the regulation of RssB activity and identify IraP as a member of a new class of regulators, the anti-adaptor proteins.