Circuitry linking the Csr and stringent response global regulatory systems

Edwards, Adrianne N.; Patterson-Fortin, Laura; Vakulskas, Christopher A.; Mercante, Jeffrey W.; Potrykus, Katarzyna; Vinella, Daniel; Camacho, Martha I.; Fields, Joshua A.; Thompson, Stuart A.; Georgellis, Dimitris; Cashel, Michael; Babitzke, Paul; Romeo, Tony

doi:10.1111/j.1365-2958.2011.07663.x

Cited by 166 publications

(336 citation statements)

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“…Single-copy, chromosomally integrated transcriptional and translational fusions to lacZ were constructed using the CRIM system (60) with plasmid vectors pLFX and pLFT, derived from pAH125 (25), and integrated into the chromosome at the att site, and single integrants were confirmed by PCR, as described previously (60).…”

Section: Methodsmentioning

confidence: 99%

“…Reciprocal regulatory interactions between the Csr and stringent response systems permit the Csr system to posttranscriptionally reinforce the transcriptional effects of DksA and (p)ppGpp on the expression of genes that are coregulated by these systems (25). Details of the interactions between the Csr and catabolite repression regulatory systems were not previously determined and are the subject of the present study.…”

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confidence: 94%

“…In Escherichia coli, CsrA activates glycolysis and central carbon pathways (7)(8)(9)(10)(11)(12)(13) and motility (14,15). Conversely, it represses gluconeogenesis (7), glycogen biosynthesis (16)(17)(18)(19)(20), biofilm formation (21)(22)(23)(24), the stringent response (25), and expression of genes involved in other stress resistance and stationary-phase processes, e.g., cstA, hfq, cel, sdiA, and nhaR (24,(26)(27)(28)(29)(30). Its effects on pathogenesis are complex.…”

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confidence: 99%

“…For example, CsrA both positively and negatively affects expression of enteropathogenic E. coli (EPEC) pathogenicity island genes (31,32). CsrA was found to copurify with over 700 different mRNAs in E. coli K-12 (25) and to affect the expression of hundreds of genes (33).…”

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confidence: 99%

“…Noteworthy among the many E. coli mRNAs that copurified with CsrA were transcripts for global regulatory factors such as relA and dksA of the stringent response system and crp and cyaA of the catabolite repression system (25). Reciprocal regulatory interactions between the Csr and stringent response systems permit the Csr system to posttranscriptionally reinforce the transcriptional effects of DksA and (p)ppGpp on the expression of genes that are coregulated by these systems (25).…”

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Circuitry Linking the Catabolite Repression and Csr Global Regulatory Systems of Escherichia coli

et al. 2016

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Cyclic AMP (cAMP) and the cAMP receptor protein (cAMP-CRP) and CsrA are the principal regulators of the catabolite repression and carbon storage global regulatory systems, respectively. cAMP-CRP controls the transcription of genes for carbohydrate metabolism and other processes in response to carbon nutritional status, while CsrA binds to diverse mRNAs and regulates translation, RNA stability, and/or transcription elongation. CsrA also binds to the regulatory small RNAs (sRNAs) CsrB and CsrC, which antagonize its activity. The BarA-UvrY two-component signal transduction system (TCS) directly activates csrB and csrC (csrB/C) transcription, while CsrA does so indirectly. We show that cAMP-CRP inhibits csrB/C transcription without negatively regulating phosphorylated UvrY (P-UvrY) or CsrA levels. A crp deletion caused an elevation in CsrB/C levels in the stationary phase of growth and increased the expression of csrB-lacZ and csrClacZ transcriptional fusions, although modest stimulation of CsrB/C turnover by the crp deletion partially masked the former effects. DNase I footprinting and other studies demonstrated that cAMP-CRP bound specifically to three sites located upstream from the csrC promoter, two of which overlapped the P-UvrY binding site. These two proteins competed for binding at the overlapping sites. In vitro transcription-translation experiments confirmed direct repression of csrC-lacZ expression by cAMP-CRP. In contrast, cAMP-CRP effects on csrB transcription may be mediated indirectly, as it bound nonspecifically to csrB DNA. In the reciprocal direction, CsrA bound to crp mRNA with high affinity and specificity and yet exhibited only modest, conditional effects on expression. Our findings are incorporated into an emerging model for the response of Csr circuitry to carbon nutritional status. IMPORTANCECsr (Rsm) noncoding small RNAs (sRNAs) CsrB and CsrC of Escherichia coli use molecular mimicry to sequester the RNA binding protein CsrA (RsmA) away from lower-affinity mRNA targets, thus eliciting major shifts in the bacterial lifestyle. CsrB/C transcription and turnover are activated by carbon metabolism products (e.g., formate and acetate) and by a preferred carbon source (glucose), respectively. We show that cAMP-CRP, a mediator of classical catabolite repression, inhibits csrC transcription by binding to the upstream region of this gene and also inhibits csrB transcription, apparently indirectly. We propose that glucose availability activates pathways for both synthesis and turnover of CsrB/C, thus shaping the dynamics of global signaling in response to the nutritional environment by poising CsrB/C sRNA levels for rapid response.T he Csr (carbon storage regulator) or Rsm (repressor of stationary-phase metabolites) system is a widely conserved bacterial posttranscriptional regulatory system (1-3). Its components, their functions, and the mechanisms by which the central regulator of this system, CsrA or RsmA, affects gene expression have been studied primarily in Gammaproteobacteria (4-6). The...

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Section: Methodsmentioning

confidence: 99%

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confidence: 94%

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confidence: 99%

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confidence: 99%

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confidence: 99%

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Circuitry Linking the Catabolite Repression and Csr Global Regulatory Systems of Escherichia coli

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RNA-mediated Control of Bacterial Gene Expression: Role of Regulatory non-Coding RNAs

Mandin

Toledo‐Arana

d’Hérouël

et al. 2013

Encyclopedia of Molecular Cell Biology and Molecular Medicine

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Evolution and Function of the RelA/SpoT Homologue (RSH) Proteins

Atkinson

Hauryliuk

2012

Encyclopedia of Life Sciences

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RelA/SpoT Homologue (RSH) proteins comprise a superfamily of enzymes that synthesise and/or hydrolyse the nucleotide alarmone ppGpp, mediator of the ‘stringent’ response and regulator of cellular metabolism in response to changing environmental conditions. Most of what we know about RSHs comes from the Escherichia coli proteins RelA and SpoT, paralogues that appear to have evolved from duplication of an ancestral Rel gene in the lineage to β‐ and γ‐proteobacteria. Recently, more details have come to light on the evolution of the RSH superfamily, revealing that there is a much greater diversity of RSHs than previously thought. Key Concepts: Various stress conditions (amino acid, iron and fatty acid starvation, heat shock, etc.) induce the so‐called ‘stringent response’ in bacteria and chloroplasts. The stringent response is mediated by RelA/SpoT Homologue (RSH) proteins that modulate intracellular concentration of the ppGpp alarmone nucleotide. ppGpp exerts its regulatory role by binding and modulating activity of several targets: the RNA polymerase, translational GTPases EF‐G and IF2, lysine decarboxylase Ldc1, polynucleotide phosphorylase, DnaG primase and others. RelA senses amino acid starvation by directly interacting with the 70S ribosome and inspecting the aminoacylation status of the A‐site tRNA, and responds to the presence of deacylated tRNA by synthesising ppGpp. SpoT is a bifunctional enzyme that has both ppGpp synthetic and hydrolytic activities and senses several cues that modulate its net activity. Phylogenetic analyses divide the RSH protein family into 30 subgroups comprising three groups: long RSHs (such as RelA and SpoT), small alarmone synthetases (SASs) and small alarmone hydrolases (SAHs). In addition to bacteria and chloroplasts, RSH proteins have been identified in eukaryotes and isolated species of archaea, however the ppGpp‐mediated stringent response has not yet been identified in these organisms. In eukaryotes, amino acid starvation is sensed by the general amino acid control (GAAC) system that is nonhomologous to the RSH system but is functionally analogous.

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Circuitry linking the Csr and stringent response global regulatory systems

Cited by 166 publications

References 84 publications

Circuitry Linking the Catabolite Repression and Csr Global Regulatory Systems of Escherichia coli

Circuitry Linking the Catabolite Repression and Csr Global Regulatory Systems of Escherichia coli

RNA-mediated Control of Bacterial Gene Expression: Role of Regulatory non-Coding RNAs

Evolution and Function of the RelA/SpoT Homologue (RSH) Proteins

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