The global, ppGpp‐mediated stringent response to amino acid starvation in <i>Escherichia coli</i>

Traxler, Matthew F.; Summers, Sean M.; Nguyen, Huyen-Tran; Zacharia, Vineetha M.; Hightower, G. Aaron; Smith, Joel T.; Conway, Tyrrell

doi:10.1111/j.1365-2958.2008.06229.x

Cited by 468 publications

(564 citation statements)

References 60 publications

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“…Recent genome-wide expression studies have reported that at least five and as many as 40 r-protein transcripts decrease following amino acid limitation (22,23). However, as in the earlier studies, conclusions about the mechanistic basis for the decrease in r-protein mRNA levels were constrained by reports that r-protein transcripts had lifetimes of only a few seconds when they were translationally repressed (24,25).…”

mentioning

confidence: 43%

Direct regulation of Escherichia coli ribosomal protein promoters by the transcription factors ppGpp and DksA

Lemke

Sanchez-Vazquez²,

Burgos³

et al. 2011

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

138

144

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We show here that the promoters for many of the Escherichia coli ribosomal protein operons are regulated directly by two transcription factors, the small RNA polymerase-binding protein DksA and the nutritional stress-induced nucleotide ppGpp. ppGpp and DksA work together to inhibit transcription initiation from ribosomal protein promoters in vitro and in vivo. The degree of promoter regulation by ppGpp/DksA varies among the r-protein promoters, but some are inhibited almost as much as rRNA promoters. Thus, many r-protein operons are regulated at the level of transcription in addition to their control by the classic translational feedback systems discovered ∼30 y ago. We conclude that direct control of r-protein promoters and rRNA promoters by the same signal, ppGpp/DksA, makes a major contribution to the balanced and coordinated synthesis rates of all of the ribosomal components.ribosome synthesis | transcriptional control | stringent response | translational control P rotein synthesis is the major consumer of cellular energy in bacteria. Because the number of ribosomes is the primary determinant of the level of translation, and ribosome synthesis itself is an energy-intensive process, there are mechanisms that prevent over-or underinvestment of cellular resources in ribosome synthesis (1). Both ribosomal RNA (rRNA) and ribosomal protein (r-protein) synthesis rates are thereby tightly regulated in Escherichia coli (for reviews, see refs. 2, 3).One of the earliest reported examples of regulation of bacterial ribosome synthesis is a stress response referred to as "the stringent response," in which rRNA transcription is inhibited in cells starved for amino acids or some other nutrients (4). In this response, uncharged tRNAs induce the ribosome-associated RelA and/or SpoT proteins to synthesize ppGpp (5-7). [The term "ppGpp" is used here to describe both the unusual nucleotide guanosine-3′,5′-(bis)pyrophosphate and its pentaphosphate precursor.] ppGpp concentrations change not only after complete starvations but also after less severe shifts in nutritional conditions, coordinating rRNA synthesis with the need for protein synthesis. Shifts to a more favorable nutritional condition result in a decrease in the concentration of ppGpp and a corresponding increase in rRNA promoter activity, whereas shifts to a less favorable condition result in an increase in ppGpp and a corresponding decrease in rRNA transcription (8).ppGpp binds directly to E. coli RNA polymerase (RNAP) and inhibits transcription from rRNA promoters (9), although the identity of the ppGpp binding site on RNAP remains unclear (10). However, for ppGpp to exert its full effect on transcription, RNAP has to be modified by the small protein, DksA (11,12). Unlike ppGpp, DksA is present at high concentrations in cells under all conditions that have been examined (11,13). rRNA transcription initiation is also regulated by the concentration of the first nucleotide in the transcript (8,14) and by at least one DNA binding factor, the 11.2-kDa Fis protein (15). Tog...

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mentioning

confidence: 43%

Direct regulation of Escherichia coli ribosomal protein promoters by the transcription factors ppGpp and DksA

Lemke

Sanchez-Vazquez²,

Burgos³

et al. 2011

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

138

144

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“…Typical reference choices for northern blot, or quantitative PCR techniques mutatis mutandis , include a ribosomal RNA (rRNA) or another RNA ( rssA , 15 idnT , 16 cysG 16 ) which is not expected to vary in cellular level from sample to sample. However, amino acid starvation triggers a major re-orchestration of the genome-wide transcription pattern 9,17,18 which results in a change in the cellular concentration of most RNA species shortly after the onset of starvation (refs. 18-20 and our manuscript in preparation).…”

Section: The Important Choice Of a Standard For Normalizationmentioning

confidence: 99%

“…However, amino acid starvation triggers a major re-orchestration of the genome-wide transcription pattern 9,17,18 which results in a change in the cellular concentration of most RNA species shortly after the onset of starvation (refs. 18-20 and our manuscript in preparation). Therefore, there is no endogenous reference transcript which is known to be suitable for comparing the cellular levels of tRNA (or any other RNA species) during amino acid starvation to the levels during steady-state growth.…”

Section: The Important Choice Of a Standard For Normalizationmentioning

confidence: 99%

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Transfer RNA instability as a stress response inEscherichia coli: Rapid dynamics of the tRNA pool as a function of demand

2018

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Production of the translation apparatus of E. coli is carefully matched to the demand for protein synthesis posed by a given growth condition. For example, the fraction of RNA polymerases that transcribe rRNA and tRNA drops from 80% during rapid growth to 24% within minutes of a sudden amino acid starvation. We recently reported in Nucleic Acids Research that the tRNA pool is more dynamically regulated than previously thought. In addition to the regulation at the level of synthesis, we found that tRNAs are subject to demand-based regulation at the level of their degradation. In this point-of-view article we address the question of why this phenomenon has not previously been described. We also present data that expands on the mechanism of tRNA degradation, and we discuss the possible implications of tRNA instability for the ability of E. coli to cope with stresses that affect the translation process.

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“…This experimentally induced nutrient limitation represents a strong stimulus 35 that could have triggered the observed response. Accordingly, both the transfer of cytoplasmic markers between cells (Fig.…”

Section: Greenmentioning

confidence: 99%

Metabolic cross-feeding via intercellular nanotubes among bacteria

et al. 2015

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Bacteria frequently exchange metabolites by diffusion through the extracellular environment, yet it remains generally unclear whether bacteria can also use cell-cell connections to directly exchange nutrients. Here we address this question by engineering cross-feeding interactions within and between Acinetobacter baylyi and Escherichia coli, in which two distant bacterial species reciprocally exchange essential amino acids. We establish that in a well-mixed environment E. coli, but likely not A. baylyi, can connect to other bacterial cells via membranederived nanotubes and use these to exchange cytoplasmic constituents. Intercellular connections are induced by auxotrophy-causing mutations and cease to establish when amino acids are externally supplied. Electron and fluorescence microscopy reveal a network of nanotubular structures that connects bacterial cells and enables an intercellular transfer of cytoplasmic materials. Together, our results demonstrate that bacteria can use nanotubes to exchange nutrients among connected cells and thus help to distribute metabolic functions within microbial communities.

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The global, ppGpp‐mediated stringent response to amino acid starvation in Escherichia coli

Cited by 468 publications

References 60 publications

Direct regulation of Escherichia coli ribosomal protein promoters by the transcription factors ppGpp and DksA

Direct regulation of Escherichia coli ribosomal protein promoters by the transcription factors ppGpp and DksA

Transfer RNA instability as a stress response inEscherichia coli: Rapid dynamics of the tRNA pool as a function of demand

Metabolic cross-feeding via intercellular nanotubes among bacteria

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