Recombinant Escherichia coli Carbon storage regulator (csrA)

A key translational regulator that binds mRNA to regulate translation initiation and/or mRNA stability, initially identified for its effects on central carbon metabolism. Mediates global changes in gene expression, shifting from rapid growth to stress survival by linking envelope stress, the stringent response and the catabolite repression systems. Binds to the 5'-UTR of mRNA to repress or activate translation; 2 binding sites on the homodimer can bridge 2 sites within target RNA. Exerts reciprocal effects on enzymes of gluconeogenesis and glycogen biosynthesis versus those of glycolysis. Negatively effects glycogen biosynthesis, gluconeogenesis, alters cell size and surface properties. Activates regulates expression of glycolysis genes. Represses biofilm formation. Regulates glycogen synthesis under both aerobic and anaerobic conditions; overexpression strongly inhibits glycogen accumulation. Binds to 4 sites in its own promoter, including the Shine-Dalgarno sequence, repressing its own translation; mutating the binding-sites decreases repression. Indirectly activates transcription from 1 of its 5 promoters, which is responsible for increased expression during stationary phase. Binds to at least 720 transcripts in strain K12 / CF7789, many of which are also part of the stringent response, including relA, spoT and dksA; slightly represses RelA and slightly activates DskA translation. Binds to and represses the ECF sigma factor rpoE promoter. Accelerates the degradation of glgC gene transcripts; overexpression further decreases glgC transcripts. Binds 2 sites in the glgC mRNA leader, 1 of which overlaps the Shine-Dalgarno sequence, preventing ribosome-binding and thus destabilizing the mRNA. Acts to inhibit interaction between the CcdB (also known as LetD) protein and the A subunit of DNA gyrase. Required to activate motility and flagellum biosynthesis through the post-transcriptional activation of flhDC expression by binding to and stabilizing the flhDC message. Represses translation of iraD mRNA via translational coupling to an upstream open reading frame. Binds to mRNA and reduces levels of probable diguanylate cyclases dgcT and dgcZ.; Binds to and is sequestered by non-coding small RNAs (sRNA) CsrB and CsrC which antagonize the activity of CsrA. The consensus RNA-binding site is CAGGA(U/A/C)G which is located in probable hairpin loops. There are 18 sites in CsrB, which cooperatively binds about 18 copies of CsrA. CsrC has 9 sites, and cooperatively binds multiple copies of CsrA. Indirectly activates expression of CsrB and CsrC, both dependently and independently of the BarA-UvrY two-component system. ppGpp activates transcription of CsrA-antagonistic small RNAs CsrB and CsrC, which downregulates CsrA's action on translation during the stringent response.