Antagonistic control of the turnover pathway for the global regulatory sRNA CsrB by the CsrA and CsrD proteins

Vakulskas, Christopher A.; Leng, Yuanyuan; Abe, Hirotake; Amaki, Takumi; Okayama, Akihiro; Babitzke, Paul; Suzuki, Kazushi; Romeo, Tony

doi:10.1093/nar/gkw484

Cited by 54 publications

(75 citation statements)

References 76 publications

(141 reference statements)

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“…10). In addition, the phosphorylation state of the PTS protein EIIA Glc serves as the key sensory mechanism for cAMP synthesis and catabolite repression control and for the turnover pathway of CsrB/C sRNAs (43,44,48). Our present data establish direct and apparently indirect connections between these two important global regulatory systems.…”

Section: Discussionmentioning

confidence: 52%

“…Degradation of CsrB and CsrC requires the protein CsrD, which facilitates endonucleolytic cleavage of these sRNAs by RNase E (42,43). Thus, the effect of CRP on synthesis of CsrB and CsrC under conditions of greatly reduced turnover was examined in a ⌬csrD strain (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…10). Transport of glucose by the PTS pathway leads to dephosphorylation of EIIA Glc , which binds to CsrD and activates the decay pathway for CsrB/C in E. coli (43,44). This kind of regulatory pathway may function in most Enterobacteriaceae, Vibrionaceae, and Shewanellaceae species and yet is absent in the majority of gammaproteobacterial families, the members of which lack a csrD homolog (42,43).…”

Section: Discussionmentioning

confidence: 99%

“…CsrA indirectly activates transcription of CsrB and CsrC through its effects on BarA-UvrY, creating a negative-feedback loop within the Csr circuitry (37,38,42). CsrB/C turnover requires the GGDEF-EAL domain protein CsrD, which is necessary for cleavage by RNase E and turnover (42,43). Therefore, CsrD affects the expression of CsrA-regulated genes and processes.…”

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confidence: 99%

“…We previously proposed a model for the influence of carbon nutrition on the workings of the Csr system based on these observations. The elimination of a preferred carbon source and the buildup of carboxylic acid products of metabolism together facilitate CsrB/C sRNA accumulation, inhibit CsrA activity, and promote the physiological switch from the exponential phase to the stationary phase of growth and a stressresistant phenotype (43,44).…”

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confidence: 99%

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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: Discussionmentioning

confidence: 52%

Section: Resultsmentioning

confidence: 99%