A trans-Acting Riboswitch Controls Expression of the Virulence Regulator PrfA in Listeria monocytogenes

Loh, Edmund; Dussurget, Olivier; Gripenland, Jonas; Vaitkevicius, Karolis; Tiensuu, Teresa; Mandin, Pierre; Repoila, Francis; Buchrieser, Carmen; Cossart, Pascale; Johansson, Jörgen

doi:10.1016/j.cell.2009.08.046

Cited by 338 publications

(318 citation statements)

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“…Furthermore, it redirects the metabolic flux through the folate synthesis pathway and increases the production of the SAM precursor, 5-methyl-tetrahydropteroyltriglutamate [23]. SAM plays an interesting dual function in the pathogenic bacterium Listeria monocytogenes, where its synthesis is monitored by up to seven classic riboswitches, which sense the SAM concentration and modulate the expression of methionine/ cysteine transporters and metabolic enzymes [49,50]. At least two of the SAM riboswitches play a second role and function as non-coding (nc)RNAs that stimulate the expression of the virulence regulator PrfA and downstream genes [50].…”

Section: Reviewmentioning

confidence: 99%

“…SAM plays an interesting dual function in the pathogenic bacterium Listeria monocytogenes, where its synthesis is monitored by up to seven classic riboswitches, which sense the SAM concentration and modulate the expression of methionine/ cysteine transporters and metabolic enzymes [49,50]. At least two of the SAM riboswitches play a second role and function as non-coding (nc)RNAs that stimulate the expression of the virulence regulator PrfA and downstream genes [50]. Thus, these SAM-binding RNA molecules perform dual functions: as riboswitches, they specifically balance SAM biosynthesis, whereas as ncRNAs, they regulate the bacterial life cycle.…”

Section: Reviewmentioning

confidence: 99%

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Regulatory crosstalk of the metabolic network

Grüning

Lehrach

Ralser

2010

Trends in Biochemical Sciences

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The metabolic network has a modular architecture, is robust to perturbations, and responds to biological stimuli and environmental conditions. Through monitoring by metabolite responsive macromolecules, metabolic pathways interact with the transcriptome and proteome. Whereas pathway interconnecting cofactors and substrates report on the overall state of the network, specialised intermediates measure the activity of individual functional units. Transitions in the network affect many of these regulatory metabolites, facilitating the parallel regulation of the timing and control of diverse biological processes. The metabolic network controls its own balance, chromatin structure and the biosynthesis of molecular cofactors; moreover, metabolic shifts are crucial in the response to oxidative stress and play a regulatory role in cancer.Evolution of the metabolic network and its structure Life probably began with the formation of compartmentalised autocatalytic chemical cycles. With the appearance of complex catalysts (ribonucleic acid-or protein-based enzymes), these cycles gained complexity, and evolved in their effectiveness and robustness [1]. These metabolic pathways now form the basis for life.As was the case for the first primitive life forms, the survival of today's complex organisms depends on the robustness and functionality of the metabolic framework [2]. To prevent and counteract perturbations in the flux, many biological control and sensor systems have evolved around the metabolic network. Metabolic pathways provide the cell with energy and supply macromolecular synthesis pathways with their required intermediates. They also balance metabolic systems under a variety of physiological conditions, and act as transducers and sensor systems for environmental conditions and stimuli. In addition, metabolic pathways are essential for crosstalk between metabolic regulatory components and the cellular transcriptome and proteome.As early as the 1960s, the principle that cells alter their gene expression in response to metabolic requirements has been known. The seminal work of Jacob and Monod, investigating the lac operon, uncovered one of the first examples of chemical-genetic regulation, by which bacterial cells adjust their enzyme production to the nutrient supply [3]. However, only recently have the broader implications of this principle emerged. Indeed, changes in the metabolic network not only control the metabolome, but they also have wide-ranging regulatory functions throughout biology.Most of the biochemical mechanisms that link the metabolic network to the transcriptome and proteome are incompletely understood. However, one type of regulation appears to be common: representative network intermediates bind to and modulate sensor function and activity of transcription factors, translational regulators, chromatin, enzymes, RNA molecules, and ion channels. Significant transcriptional changes around these intermediates identified them as reporter metabolites [4,5]. The use of intermediates as activity reporters ne...

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Section: Reviewmentioning

confidence: 99%

Section: Reviewmentioning

confidence: 99%

Regulatory crosstalk of the metabolic network

Grüning

Lehrach

Ralser

2010

Trends in Biochemical Sciences

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“…The expression is simultaneously controlled by a RNA thermosensor mechanism, that allows translation at 37°C, and by a trans-acting riboswitch. 184,185 The activity is presumably regulated through cofactor-mediated allosteric shift. This putative PrfA cofactor is yet to be identified, but links between carbon metabolism and PrfA-dependent transcription suggest that host nutrient availability may work as an intracellular localization signal for L. monocytogenes.…”

Section: O N O T D I S T R I B U T Ementioning

confidence: 99%

The arsenal of virulence factors deployed byListeria monocytogenesto promote its cell infection cycle

et al. 2011

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“…11,[30][31][32][33][34] These riboswitches are located upstream of genes involved in the metabolism, biosynthesis and transport of methionine or SAM. 11,35 The SAM riboswitch class is one of the most abundant, 36 especially in Gram-positive organisms, and is unique in that six distinct SAM riboswitch families have been reported to date that bind SAM in diverse ways.…”

Section: S-adenosylmethionine (Sam) Riboswitchesmentioning

confidence: 99%