Decline in ribosomal fidelity contributes to the accumulation and stabilization of the master stress response regulator sigmaS upon carbon starvation.
The sigma(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 sigma(S) levels and stability. Furthermore, mutations enhancing translational fidelity attenuate induction of the rpoS regulon and prevent stabilization of sigma(S) upon carbon starvation. Destabilization of sigma(S) by increased proofreading requires the presence of the sigma(S) recognition factor SprE (RssB) and the ClpXP protease. The data further suggest that sigma(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 sigma(S), whereas overproduction of a ClpXP substrate (ssrA-tagged GFP) stabilized sigma(S) in exponentially growing cells. We present a model for the sequence of events leading to the accumulation and activation of sigma(S) upon carbon starvation, which are linked to alterations in both ribosomal fidelity and efficiency.
Fredriksson
Asa
A
Department of Cell and Molecular Biology-Microbiology, Göteborg University, 405 30 Göteborg, Sweden.
Ballesteros
Manuel
M
Peterson
Celeste N
CN
Persson
Orjan
O
Silhavy
Thomas J
TJ
Nyström
Thomas
T
D001426:Bacterial Proteins / Q000378:metabolism*; D002244:Carbon / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D049071:Endopeptidase Clp / Q000378:metabolism; D004795:Enzyme Stability; D004926:Escherichia coli / Q000235:genetics*; D029968:Escherichia coli Proteins / Q000378:metabolism; D008954:Models, Biological; D010084:Oxidation-Reduction; D018085:Regulon; D012270:Ribosomes / Q000378:metabolism*; D012808:Sigma Factor / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism
D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; D012808:Sigma Factor; D014157:Transcription Factors; C098923:rssB protein, E coli; C069567:sigma factor KatF protein, Bacteria; D002244:Carbon; C483572:ClpP protease, E coli; D049071:Endopeptidase Clp