GUANOSINE TETRAPHOSPHATE AS A GLOBAL REGULATOR OF BACTERIAL RNA-SYNTHESIS - A MODEL INVOLVING RNA-POLYMERASE PAUSING AND QUEUING

A recently reported comparison of stable RNA (rRNA, tRNA) and mRNA syn thesis rates in ppGpp-synthesizing and ppGpp-deficient (Delta relA Del ta spoT) bacteria has suggested that ppGpp inhibits transcription init iation from stable RNA promoters, as well as synthesis of (bulk) mRNA. Inhibition of stable RNA synthesis occurs mainly during slow growth o f bacteria when cytoplasmic levels of ppGpp are high. In contrast, inh ibition of mRNA occurs mainly during fast growth when ppGpp levels are low, and it is associated with a partial inactivation of RNA polymera se. To explain these observations it has been proposed that ppGpp caus es transcriptional pausing and queuing during the synthesis of mRNA. P olymerase queuing requires high rates of transcription initiation in a ddition to polymerase pausing, and therefore high concentrations of fr ee RNA polymerase. These conditions are found in fast growing bacteria . Furthermore, the RNA polymerase queues lead to a promoter blocking w hen RNA polymerase molecules stack up from the pause site back to the (mRNA) promoter. This occurs most frequently at pause sites close to t he promoter. Blocking of mRNA promoters diverts RNA polymerase to stab le RNA promoters, In this manner ppGpp could indirectly stimulate synt hesis of stable RNA at high growth rates. In the present work a mathem atical analysis, based on the theory of queuing, is presented and appl ied to the global control of transcription in bacteria. This model pre dicts the in vivo distribution of RNA polymerase over stable RNA and m RNA genes for both ppGpp-synthesizing and ppGpp-deficient bacteria in response to different environmental conditions. It also shows how smal l changes in basal ppGpp concentrations can produce large changes in t he rate of stable RNA synthesis.