Down-regulation of outer membrane proteins by noncoding RNAs: unraveling the cAMP-CRP- and sigmaE-dependent CyaR-ompX regulatory case.
The sigma(E) (extracytoplasmic stress response sigma factor in Escherichia coli) signaling system of Gram-negative bacteria plays an essential role in the maintenance of the extracytoplasmic compartment. Upon induction of this system, approximately 100 genes are up-regulated. The majority of these genes encode proteins that participate in the synthesis, assembly, and homeostasis of outer membrane proteins and lipopolysaccharides. A second aspect of the sigma(E) response is a regulatory loop that prevents expression of the major porins. Misfolding or overproduction of most of these porins is sufficient to trigger the envelope stress response. Recent work indicates that small Hfq-binding RNAs play a major role in maintaining envelope homeostasis and, so far, two sigma(E)-dependent small noncoding RNAs (sRNAs), MicA and RybB, have been shown to facilitate rapid removal of multiple omp transcripts in response to elevated activity of the alternative sigma factor. Here we report the identification of the sRNA (CyaR, cyclic AMP-activated RNA) that promotes decay of the ompX mRNA. The transcription of the cyaR gene is stringently controlled by cAMP-cAMP receptor protein and, unexpectedly, cyaR expression is also up-regulated, directly or indirectly, by sigma(E). In addition, this work identified MicA as a factor that cooperates in the negative control of ompX expression. The conservation of CyaR, MicA, RybB, and their targets suggests that the omp mRNA-sRNA regulatory network is an integral part of the envelope stress response in many enterobacteria.
Johansen
Jesper
J
Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense M, Denmark.
Eriksen
Maiken
M
Kallipolitis
Birgitte
B
Valentin-Hansen
Poul
P
D001425:Bacterial Outer Membrane Proteins / Q000235:genetics* / Q000378:metabolism*; D001483:Base Sequence; D000242:Cyclic AMP / Q000378:metabolism; D002373:Cyclic AMP Receptor Protein / Q000235:genetics* / Q000378:metabolism*; D045647:DNA Glycosylases / Q000235:genetics / Q000378:metabolism; D004269:DNA, Bacterial / Q000235:genetics; D015536:Down-Regulation; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000235:genetics* / Q000378:metabolism*; D005798:Genes, Bacterial; D035001:Host Factor 1 Protein / Q000235:genetics / Q000378:metabolism; D006867:Hydrolases / Q000235:genetics* / Q000378:metabolism*; D008954:Models, Biological; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D012329:RNA, Bacterial / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D022661:RNA, Untranslated / Q000235:genetics* / Q000378:metabolism*; D012689:Sequence Homology, Nucleic Acid; D012808:Sigma Factor / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction
D001425:Bacterial Outer Membrane Proteins; D002373:Cyclic AMP Receptor Protein; D004269:DNA, Bacterial; D029968:Escherichia coli Proteins; C087373:Hfq protein, E coli; D035001:Host Factor 1 Protein; D012329:RNA, Bacterial; D012333:RNA, Messenger; D022661:RNA, Untranslated; D012808:Sigma Factor; C481662:crp protein, E coli; C063202:sporulation-specific sigma factors; C482905:OmpX protein, E coli; D000242:Cyclic AMP; D006867:Hydrolases; D045647:DNA Glycosylases; C061738:mutY adenine glycosylase