Decline in ribosomal fidelity contributes to the accumulation and stabilization of the master stress response regulator σS upon carbon starvation

Abstract

The σ^S subunit of RNA polymerase is a master regulator of Escherichia coli that retards cellular senescence and bestows cells with general stress protective functions during growth arrest. We show that mutations and drugs triggering translational errors elevate σ^S levels and stability. Furthermore, mutations enhancing translational fidelity attenuate induction of the rpoS regulon and prevent stabilization of σ^S upon carbon starvation. Destabilization of σ^S by increased proofreading requires the presence of the σ^S recognition factor SprE (RssB) and the ClpXP protease. The data further suggest that σ^S becomes stabilized upon starvation as a result of ClpP sequestration and this sequestration is enhanced by oxidative modifications of aberrant proteins produced by erroneous translation. ClpP overproduction counteracted starvation-induced stabilization of σ^S, whereas overproduction of a ClpXP substrate (ssrA-tagged GFP) stabilized σ^S in exponentially growing cells. We present a model for the sequence of events leading to the accumulation and activation of σ^S upon carbon starvation, which are linked to alterations in both ribosomal fidelity and efficiency.