Regulation of carbamoylphosphate synthesis in Escherichia coli: an amazing metabolite at the crossroad of arginine and pyrimidine biosynthesis

Charlier, Daniël; Minh, Phu Nguyen Le; Roovers, Martine

doi:10.1007/s00726-018-2654-z

Cited by 36 publications

(25 citation statements)

References 186 publications

(239 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similar to OppBCDF, the CarAB complex contains one subunit of CarA and one subunit of CarB. Transcriptional control of carAB is complex and controlled by several transcription factors integrating information from purine, pyrimidine, and arginine pathways ( Charlier et al, 2018 ). While the exact biological role of CarZ-mediated feedback regulation of carAB requires further investigation, transcription factor-based feedback regulation has been reported to reduce transcriptional noise ( Alon, 2007 ), which could also be an important feature of sRNA-mediated autoregulation.…”

Section: Discussionmentioning

confidence: 99%

Gene autoregulation by 3’ UTR-derived bacterial small RNAs

Hoyos

Huber

Förstner

et al. 2020

eLife

View full text Add to dashboard Cite

Negative feedback regulation, that is the ability of a gene to repress its own synthesis, is the most abundant regulatory motif known to biology. Frequently reported for transcriptional regulators, negative feedback control relies on binding of a transcription factor to its own promoter. Here, we report a novel mechanism for gene autoregulation in bacteria relying on small regulatory RNA (sRNA) and the major endoribonuclease, RNase E. TIER-seq analysis (transiently-inactivating-an-endoribonuclease-followed-by-RNA-seq) revealed ~25,000 RNase E-dependent cleavage sites in Vibrio cholerae, several of which resulted in the accumulation of stable sRNAs. Focusing on two examples, OppZ and CarZ, we discovered that these sRNAs are processed from the 3’ untranslated region (3’ UTR) of the oppABCDF and carAB operons, respectively, and base-pair with their own transcripts to inhibit translation. For OppZ, this process also triggers Rho-dependent transcription termination. Our data show that sRNAs from 3’ UTRs serve as autoregulatory elements allowing negative feedback control at the post-transcriptional level.

show abstract

Section: Discussionmentioning

confidence: 99%

Gene autoregulation by 3’ UTR-derived bacterial small RNAs

Hoyos

Huber

Förstner

et al. 2020

eLife

View full text Add to dashboard Cite

show abstract

“…Besides this complex regulation by multiple bona fide TFs and trigger enzymes, P1 is subject to stringent control (ppGpp) (Bouvier, Patte and Stragier 1984) and UTP-dependent RNAP stuttering (Han and Turnbough 1998) (see below for the mechanism of RNAP stuttering). For a complete overview of carAB regulation, see Charlier, Nguyen Le Minh and Roovers (2018).…”

Section: Introductionmentioning

confidence: 99%

Diversity, versatility and complexity of bacterial gene regulation mechanisms: opportunities and drawbacks for applications in synthetic biology

Bervoets

Charlier

2019

FEMS Microbiology Reviews

Self Cite

132

101

View full text Add to dashboard Cite

Gene expression occurs in two essential steps: transcription and translation. In bacteria, the two processes are tightly coupled in time and space, and highly regulated. Tight regulation of gene expression is crucial. It limits wasteful consumption of resources and energy, prevents accumulation of potentially growth inhibiting reaction intermediates, and sustains the fitness and potential virulence of the organism in a fluctuating, competitive and frequently stressful environment. Since the onset of studies on regulation of enzyme synthesis, numerous distinct regulatory mechanisms modulating transcription and/or translation have been discovered. Mostly, various regulatory mechanisms operating at different levels in the flow of genetic information are used in combination to control and modulate the expression of a single gene or operon. Here, we provide an extensive overview of the very diverse and versatile bacterial gene regulatory mechanisms with major emphasis on their combined occurrence, intricate intertwinement and versatility. Furthermore, we discuss the potential of well-characterized basal expression and regulatory elements in synthetic biology applications, where they may ensure orthogonal, predictable and tunable expression of (heterologous) target genes and pathways, aiming at a minimal burden for the host.

show abstract

“…As shown above, the ARG boxes in the lrp control region are located downstream of the transcription start site. In this context, it is worth noticing that ArgR binding to the ARG boxes overlapping the E. coli car P2 promoter strongly represses transcription initiation from this promoter but does not hinder transcription initiated 67 nt more upstream at the car P1 promoter (Charlier et al, 1988, 2018). Hence, it appears that ArgR is unable to function as an efficient roadblock for an elongating RNA polymerase.…”

Section: Resultsmentioning

confidence: 99%

Competitive Repression of the artPIQM Operon for Arginine and Ornithine Transport by Arginine Repressor and Leucine-Responsive Regulatory Protein in Escherichia coli

et al. 2019

Self Cite

View full text Add to dashboard Cite

Two out of the three major uptake systems for arginine in Escherichia coli are encoded by the artJ - artPIQM gene cluster. ArtJ is the high-affinity periplasmic arginine-specific binding protein (ArgBP-I), whereas artI encodes the arginine and ornithine periplasmic binding protein (AO). Both ArtJ and ArtI are supposed to combine with the inner membrane-associated ArtQMP 2 transport complex of the ATP-binding cassette-type (ABC). Transcription of artJ is repressed by arginine repressor (ArgR) and the artPIQM operon is regulated by the transcriptional regulators ArgR and Leucine-responsive regulatory protein (Lrp). Whereas repression by ArgR requires arginine as corepressor, repression of P artP by Lrp is partially counteracted by leucine, its major effector molecule. We demonstrate that binding of dimeric Lrp to the artP control region generates four complexes with a distinct migration velocity, and that leucine has an effect on both global binding affinity and cooperativity in the binding. We identify the binding sites for Lrp in the artP control region, reveal interferences in the binding of ArgR and Lrp in vitro and demonstrate that the two transcription factors act as competitive repressors in vivo , each one being a more potent regulator in the absence of the other. This competitive behavior may be explained by the partial steric overlap of their respective binding sites. Furthermore, we demonstrate ArgR binding to an unusual position in the control region of the lrp gene, downstream of the transcription initiation site. From this unusual position for an ArgR-specific operator, ArgR has little direct effect on lrp expression, but interferes with the negative leucine-sensitive autoregulation exerted by Lrp. Direct arginine and ArgR-dependent repression of lrp could be observed with a 25-bp deletion mutant, in which the ArgR binding site was artificially moved to a position immediately downstream of the lrp transcription initiation site. This finding is reminiscent of a previous observation made for the carAB operon encoding carbamoylphosphate synthase, where ArgR bound in overlap with the downstream promoter P2 does not block transcription initiated 67 bp upstream at the P1 promoter, and further supports the hypothesis that ArgR does not act as an efficient roadblock.

show abstract

Regulation of carbamoylphosphate synthesis in Escherichia coli: an amazing metabolite at the crossroad of arginine and pyrimidine biosynthesis

Cited by 36 publications

References 186 publications

Gene autoregulation by 3’ UTR-derived bacterial small RNAs

Gene autoregulation by 3’ UTR-derived bacterial small RNAs

Diversity, versatility and complexity of bacterial gene regulation mechanisms: opportunities and drawbacks for applications in synthetic biology

Competitive Repression of the artPIQM Operon for Arginine and Ornithine Transport by Arginine Repressor and Leucine-Responsive Regulatory Protein in Escherichia coli

Contact Info

Product

Resources

About