E. coli's 6S RNA is a type of noncoding, small RNA that is ubiquitously expressed in the cell and is the key component in a unique global RNA polymerase (RNAP) - mediated regulation mechanism. 6S RNA was shown to differentially inhibit σ-70 dependent promoters during stationary phase by binding and forming a stable complex with the housekeeping form of RNAP, blocking the ability of RNAP to bind to promoter DNA. Surprisingly, when stationary phase cells are exposed to high enough levels of nucleotide-triphosphate (NTP), they enter outgrowth phase at which time 6S RNA is used as a template for product RNA (pRNA) synthesis. 6S RNA interactions with RNAP are destabilized during the pRNA synthesis reaction, leading to the dissociation of the 6S RNA-RNAP complexes. The released 6S RNA becomes highly unstable and the released RNAP enables increased transcription of genes [1-3]. Many of the dynamic properties and the unexpected promoter specificity which characterize this regulation mechanism are still unclear.

Using a mathematical model of this biological system we study the dynamics of the system components and specifically mRNAs transcribed by σ-70 dependent promoters (during exponential phase, stationary phase and outgrowth) [4]. We find that this global regulation mechanism exhibits unique properties; RNAP level returns to steady state subsequent to its inhibition, and stored inactive RNAPs bound by 6S RNA accumulate over late stationary phase and can return to their active form rapidly upon the introduction of newly available nutrients. Interestingly, although 6S RNA inhibits the general transcription machinery, genes with σ-70 dependent promoters exhibit variable sensitivities to this regulation. We demonstrate that the specific regulation of genes by 6S RNA depends on their inherent effective promoter parameters- affinity to RNAP and clearance rate.  We also compare 6S RNA regulation to other global RNAP-mediated regulation mechanisms and deduce several of its key properties, including its energetic efficiency, its robustness to noise, and the competitive edge of cells carrying it at the transition to a new environment.