Csr is a conserved global regulatory system, which uses the sequence-specific RNA-binding protein CsrA to activate or repress gene expression by binding to mRNA and altering translation, stability and/or transcript elongation. InEscherichia coli, CsrA activity is regulated by two sRNAs, CsrB and CsrC, which bind to multiple CsrA dimers, thereby sequestering this protein away from its mRNA targets. Turnover of CsrB/C sRNAs is tightly regulated by a GGDEF-EAL domain protein, CsrD, which targets them for cleavage by RNase E. Here, we show that EIIAGlc of the glucose-specific PTS system is also required for the normal decay of these sRNAs and that it acts by binding to the EAL domain of CsrD. Only the unphosphorylated form of EIIAGlc bound to CsrDin vitroand was capable of activating CsrB/C turnoverin vivo. Genetic studies confirmed that this mechanism couples CsrB/C sRNA decay to the availability of a preferred carbon source. These findings reveal a new physiological influence on the workings of the Csr system, a novel function for the EAL domain, and an important new way in which EIIAGlc shapes global regulatory circuitry in response to nutritional status.
We demonstrate a novel global regulatory function for EIIAGlc of the PTS pathway. In the presence of glucose, EIIAGlc becomes dephosphorylated and able to bind to the GGDEF-EAL domain protein CsrD, which activates the turnover of CsrB/C sRNAs. Because CsrB/C sequester the RNA binding protein CsrA away from its lower affinity mRNA targets, this mechanism should enhance CsrA availability when it is needed for rapid growth and restrict its availability when stress resistance is paramount.