Histidine regulation in Salmonella typhimurium: an activator attenuator model of gene regulation.

Artz, S W; Broach, James R.

doi:10.1073/pnas.72.9.3453

Cited by 95 publications

(57 citation statements)

References 28 publications

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“…Studies on the regulation of the his operon of S. typhimurium, a gene cluster that may have a similar mechanism of termination control, indicate that translation is a prerequisite for transcription (26), a situation contrary to the one we suggest for the trp operon.…”

Section: Methodsmentioning

confidence: 51%

Transcription termination at the trp operon attenuators of Escherichia coli and Salmonella typhimurium: RNA secondary structure and regulation of termination.

Lee¹,

Yanofsky²

1977

Proc. Natl. Acad. Sci. U.S.A.

219

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Transcription termination at the attenuators of the trp operons of Escherichia coli and Salmonella typhimurium was studied in vitro using DNA restriction fragments as templates. Readthrough transcription beyond the terminators occurred with 5 and 30% efficiency, respectively, in E. coli and S. typhimurium. This difference is correlated with the stability of proposed secondary structures of the respective trp leader transcripts. Secondary structure analyses of the two leader transcripts revealed a well-conserved pattern of RNA base pairing. This and the possibility that trp leader RNA is translated suggest a model for regulation of transcription termination that is based on ribosome movement along the RNA and a shift between alternative RNA base-pairing configurations.The tryptophan (trp) operon of Escherichia coli has two transcription control sites, a promoter-operator (14) and an attenuator (4). At the attenuator, a site located in the transcribed leader segment of the operon, transcription is either terminated or allowed to continue into the structural genes of the operon (4). Transcription termination at the attenuator appears to be regulated in response to changes in the extent of charging of tRNATrP (5, 6). Salmonella typhimurium has a trp attenuator that functions much like the one in E. coil (F. Lee and C. Yanofsky, unpublished). The sequences of the leader-attenuator regions of the trp operons of both species have been determined (F. Lee, K. Bertrand, G. Bennett, and C. Yanofsky, unpublished.In this paper we report the results of in vitro transcription studies with restriction fragments of the tip operons of both organisms. We show that the tip leader transcripts have appreciable secondary structure. We suggest how this structure may play a role in regulating transcription termination at the attenuator. MATERIALS AND METHODSRestriction fragments of the E. coli and S. typhimurium trp operons were derived from plasmids pVH153 (7) mM Tris, pH 7.9/10 mM MgCl2/0.1 mM EDTA, and RNase T1 was added to a final concentration of 10 units/ml. Incubations were carried out at 200. Samples were withdrawn at various times, chilled, and then diluted with the same buffer. Diethylpyrocarbonate was added to 1% before the samples were precipitated with ethanol in the presence of carrier tRNA. They were then dissolved in urea/dye solution and loaded on denaturing gels. RNA fragments were eluted from polyacrylamide gels, digested to completion with RNase T1, and fingerprinted (11).All procedures using recombinant DNA were performed in accordance with the National Institutes of Health Guidelines. RESULTS Transcription Termination on trp Operon Restriction Fragments. Previous studies in vitro established that when purified RNA polymerase transcribes the trp operon of E. coli, it generally terminates transcription after synthesizing the first 140 residues of trp RNA (12). The 3'-OH termini of the in vitro RNA transcripts are at about the same position as the termini of the in vivo transcripts (13). Thus, in vitro, RNA ...

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Section: Methodsmentioning

confidence: 51%

Transcription termination at the trp operon attenuators of Escherichia coli and Salmonella typhimurium: RNA secondary structure and regulation of termination.

Lee¹,

Yanofsky²

1977

Proc. Natl. Acad. Sci. U.S.A.

219

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“…With respect to the conversion of uridine into pseudouridine, we know that it always occurs (tRNAVal is probably a special case) but it is not essential for the function of tRNA as adaptor of aminoacids. HisT mutant tRNA's which lack pseudouridine in this region functions perfectly well in the aminoacylation reaction and in protein synthesis (17,18). On the other hand these mutant tRNA are unable to participate in the transcriptional regulation of several operons (10,12), suggesting that pseudouridine is important for the role of tRNA in regulation (19).…”

Section: Discussionmentioning

confidence: 99%

Purification of pseudouridylate synthetase I from Salmonella typhimurium

et al. 1978

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“…To achieve this regulation, a variety of strategies can be used, involving different interplay between metabolites, enzymes, and regulatory proteins. In many cases involving model organisms, the regulatory framework that controls this process is known, and research over past decades has revealed a number of different regulatory strategies (1)(2)(3)(4).…”

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confidence: 99%

Regulatory architecture determines optimal regulation of gene expression in metabolic pathways

Chubukov

Zuleta

2012

Proc. Natl. Acad. Sci. U.S.A.

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In response to environmental changes, the connections ("arrows") in gene regulatory networks determine which genes modulate their expression, but the quantitative parameters of the network ("the numbers on the arrows") are equally important in determining the resulting phenotype. What are the objectives and constraints by which evolution determines these parameters? We explore these issues by analyzing gene expression changes in a number of yeast metabolic pathways in response to nutrient depletion. We find that a striking pattern emerges that couples the regulatory architecture of the pathway to the gene expression response. In particular, we find that pathways controlled by the intermediate metabolite activation (IMA) architecture, in which an intermediate metabolite activates transcription of pathway genes, exhibit the following response: the enzyme immediately downstream of the regulatory metabolite is under the strongest transcriptional control, whereas the induction of the enzymes upstream of the regulatory intermediate is relatively weak. This pattern of responses is absent in pathways not controlled by an IMA architecture. The observation can be explained by the constraint imposed by the fundamental feedback structure of the network, which places downstream enzymes under a negative feedback loop and upstream ones under a positive feedback loop. This general design principle for transcriptional control of a metabolic pathway can be derived from a simple cost/benefit model of gene expression, in which the observed pattern is an optimal solution. Our results suggest that the parameters regulating metabolic enzyme expression are optimized by evolution, under the strong constraint of the underlying regulatory architecture.A classic paradigm of gene regulation is the regulation of metabolic enzyme expression in response to changes in external nutrient levels. By regulating enzyme levels, cells not only control the metabolic program, but also save resources and energy by not expressing enzymes that are not needed at a particular time. To achieve this regulation, a variety of strategies can be used, involving different interplay between metabolites, enzymes, and regulatory proteins. In many cases involving model organisms, the regulatory framework that controls this process is known, and research over past decades has revealed a number of different regulatory strategies (1-4).For a linear biosynthetic pathway, a general strategy for controlling the pathway flux is end product feedback inhibition, typically acting on the first enzyme of the pathway (Fig. 1 B-D) and serving as the main sensor of product depletion. In addition, the expression of enzymes is often controlled at the transcriptional level, by transcription factors (TFs) that can sense either the end product or an intermediate metabolite, giving rise to different regulatory architectures (Fig.

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Histidine regulation in Salmonella typhimurium: an activator attenuator model of gene regulation.

Cited by 95 publications

References 28 publications

Transcription termination at the trp operon attenuators of Escherichia coli and Salmonella typhimurium: RNA secondary structure and regulation of termination.

Transcription termination at the trp operon attenuators of Escherichia coli and Salmonella typhimurium: RNA secondary structure and regulation of termination.

Purification of pseudouridylate synthetase I from Salmonella typhimurium

Regulatory architecture determines optimal regulation of gene expression in metabolic pathways

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