Promoter-specific control of <i>E. coli</i> RNA polymerase by ppGpp and a general transcription factor

Roberts, Jeffrey W.

doi:10.1101/gad.1770509

Cited by 13 publications

(11 citation statements)

References 35 publications

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“…Stringent response regulation of glycerol and chitobiose gene expression might be mediated directly at the level of transcription by interactions of (p)ppGpp and DksA with the RNA polymerase complex at the glycerol and chitobiose gene promoters [ 1 , 14 , 83 ]. That there were no differences in transcriptional levels of rpoS , rpoN , bosR , and rrp2 between the rel Bbu mutant and wild type B .…”

Section: Discussionmentioning

confidence: 99%

“…That there were no differences in transcriptional levels of rpoS , rpoN , bosR , and rrp2 between the rel Bbu mutant and wild type B . burgdorferi under any experimental conditions examined suggests a direct interaction of (p)ppGpp with the RNA polymerase complexes at the glp and chitobiose operon promoters or interactions with still uncharacterized regulators [ 1 , 14 , 48 , 50 , 83 ]. The B .…”

Section: Discussionmentioning

confidence: 99%

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Characterization of the RelBbu Regulon in Borrelia burgdorferi Reveals Modulation of Glycerol Metabolism by (p)ppGpp

et al. 2015

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The bacterial stringent response is triggered by deficiencies of available nutrients and other environmental stresses. It is mediated by 5'-triphosphate-guanosine-3'-diphosphate and 5'-diphosphate-guanosine-3'-diphosphate (collectively (p)ppGpp) and generates global changes in gene expression and metabolism that enable bacteria to adapt to and survive these challenges. Borrelia burgdorferi encounters multiple stressors in its cycling between ticks and mammals that could trigger the stringent response. We have previously shown that the B. burgdorferi stringent response is mediated by a single enzyme, RelBbu, with both (p)ppGpp synthase and hydrolase activities, and that a B. burgdorferi 297 relBbu null deletion mutant was defective in adapting to stationary phase, incapable of down-regulating synthesis of rRNA and could not infect mice. We have now used this deletion mutant and microarray analysis to identify genes comprising the rel regulon in B. burgdorferi cultured at 34°C, and found that transcription of genes involved in glycerol metabolism is induced by rel Bbu. Culture of the wild type parental strain, the rel Bbu deletion mutant and its complemented derivative at 34°C and 25°C in media containing glucose or glycerol as principal carbon sources revealed a growth defect in the mutant, most evident at the lower temperature. Transcriptional analysis of the glp operon for glycerol uptake and metabolism in these three strains confirmed that rel Bbu was necessary and sufficient to increase transcription of this operon in the presence of glycerol at both temperatures. These results confirm and extend previous findings regarding the stringent response in B. burgdorferi. They also demonstrate that the stringent response regulates glycerol metabolism in this organism and is likely crucial for its optimal growth in ticks.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Characterization of the RelBbu Regulon in Borrelia burgdorferi Reveals Modulation of Glycerol Metabolism by (p)ppGpp

et al. 2015

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“…In a view of the fact that DksA enhances negative and positive effects of ppGpp on promoters’ activities, it was proposed that DksA plays a role as a cofactor of the stringent response (6–8,15). Nevertheless, recent reports indicated that DksA and ppGpp can have independent or opposing effects (16–20) or their effects may very specifically depend on the individual promoters, holoenzymes involved or stress conditions (21).…”

Section: Introductionmentioning

confidence: 99%

The dual role of DksA protein in the regulation ofEscherichia colipArgX promoter

et al. 2016

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Gene expression regulation by the stringent response effector, ppGpp, is facilitated by DksA protein; however DksA and ppGpp can play independent roles in transcription. In Escherichia coli, the pArgX promoter which initiates the transcription of four tRNA genes was shown to be inhibited by ppGpp. Our studies on the role of DksA in pArgX regulation revealed that it can stimulate transcription by increasing the binding of RNA polymerase to the promoter and the productive transcription complex formation. However, when DksA is present together with ppGpp a severe down-regulation of promoter activity is observed. Our results indicate that DksA facilitates the effects of ppGpp to drive formation of inactive dead-end complexes formed by RNA polymerase at the ArgX promoter. In vivo, ppGpp-mediated regulation of pArgX transcription is dependent on DksA activity. The potential mechanisms of opposing pArgX regulation by ppGpp and DksA are discussed. pArgX is the first reported example of the promoter stimulated by DksA and inhibited by ppGpp in vitro when an overall inhibition occurs in the presence of both regulators. A dual role is thus proposed for DksA in the regulation of the pArgX promoter activity.

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“…Studies have shown that the accumulation of unusual guanosine nucleotides, collectively called (p)ppGpp, is the hallmark of the stringent response of E. coli [15-18] (Figure 1). Such accumulation is known to be controlled by the activity of two enzymes, the ribosome-bound RelA enzyme (ppGpp synthetase I) that synthesises (p)ppGpp nucleotides upon the depletion of amino acids [19] and the bifunctional SpoT enzyme (ppGpp synthetase II) that is responsible for maintaining the intracellular levels of (p)ppGpp nucleotides via enzymatic degradation [20].…”

Section: Introductionmentioning

confidence: 99%

Stringent response of Escherichia coli: revisiting the bibliome using literature mining

Carneiro

Lourenço

Ferreira

et al. 2011

Microb Informatics Exp

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BackgroundUnderstanding the mechanisms responsible for cellular responses depends on the systematic collection and analysis of information on the main biological concepts involved. Indeed, the identification of biologically relevant concepts in free text, namely genes, tRNAs, mRNAs, gene products and small molecules, is crucial to capture the structure and functioning of different responses.ResultsIn this work, we review literature reports on the study of the stringent response in Escherichia coli. Rather than undertaking the development of a highly specialised literature mining approach, we investigate the suitability of concept recognition and statistical analysis of concept occurrence as means to highlight the concepts that are most likely to be biologically engaged during this response. The co-occurrence analysis of core concepts in this stringent response, i.e. the (p)ppGpp nucleotides with gene products was also inspected and suggest that besides the enzymes RelA and SpoT that control the basal levels of (p)ppGpp nucleotides, many other proteins have a key role in this response. Functional enrichment analysis revealed that basic cellular processes such as metabolism, transcriptional and translational regulation are central, but other stress-associated responses might be elicited during the stringent response. In addition, the identification of less annotated concepts revealed that some (p)ppGpp-induced functional activities are still overlooked in most reviews.ConclusionsIn this paper we applied a literature mining approach that offers a more comprehensive analysis of the stringent response in E. coli. The compilation of relevant biological entities to this stress response and the assessment of their functional roles provided a more systematic understanding of this cellular response. Overlooked regulatory entities, such as transcriptional regulators, were found to play a role in this stress response. Moreover, the involvement of other stress-associated concepts demonstrates the complexity of this cellular response.

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Promoter-specific control of E. coli RNA polymerase by ppGpp and a general transcription factor

Cited by 13 publications

References 35 publications

Characterization of the RelBbu Regulon in Borrelia burgdorferi Reveals Modulation of Glycerol Metabolism by (p)ppGpp

Characterization of the RelBbu Regulon in Borrelia burgdorferi Reveals Modulation of Glycerol Metabolism by (p)ppGpp

The dual role of DksA protein in the regulation ofEscherichia colipArgX promoter

Stringent response of Escherichia coli: revisiting the bibliome using literature mining

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