Two Compounds implicated in the Function of the RC Gene of Escherichia coli

Cashel, Michael; Gallant, Jonathan

doi:10.1038/221838a0

Cited by 736 publications

(453 citation statements)

References 19 publications

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“…The stringent response can be further characterized, as shown by Cashell and Gallant (6,8), by the accumulation of ppGpp and ppGppp. These investigators have suggested that as protein synthesis is inhibited (idles) ppGpp and ppGppp are produced, and that it is the accumulation of these compounds that may regulate rRNA synthesis.…”

Section: Discussionmentioning

confidence: 99%

“…The accumulation of ppGpp is invariably observed in the absence of stable RNA synthesis (6,7,(15)(16)(17)(18)(19). Therefore, ppGpp accumulation should be observed in either strain 5F2-rel+ or 10B6 (both rel+) at either 42°or 30°when protein synthesis is inhibited.…”

Section: Synthesis Of Ppgpp and Gtpmentioning

confidence: 99%

“…More recently, Cashel and Gallant (6)(7)(8) identified two unusual guanosine nucleotides, guanosine tetraphosphate and guanosine pentaphosphate (MSI and MSII, respectively), that accumulate during the inhibition of protein synthesis in a stringent strain, but not in a relaxed strain. It was suggested (8) that accumulated ppGpp and/or ppGppp inhibit(s) stable RNA synthesis.…”

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confidence: 99%

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Synthesis of Stable RNA in Stringent Escherichia coli Cells in the Absence of Charged Transfer RNA

Kaplan

Atherly

Barrett

1973

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

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It has been possible to demonstrate the complete absence of either charged tRNAGlu or charged tRNAVal at 420 by the use of two stringent strains of E. coli, one temperature-sensitive for glutamyl-tRNA synthetase and the other temperature-sensitive for valyltRNA synthetase. In both strains, stable RNA synthesis ceases, and guanosine tetraphosphate accumulates upon incubation at the nonpermissive temperature. Unique among a series of antibiotics tested, only tetracycline was able to stimulate stable RNA synthesis and to cause disappearance of the guanosine nucleotide. In this regard tetracycline and the "relaxed" gene product appear to be analogous.The synthesis of stable RNA is greatly diminished when Escherichia coli is unable to synthesize protein as the result of either a nutritional or mutational block. This linkage between protein and RNA synthesis has been termed the stringent response, and is directly or indirectly dependent upon a functional rel+ allele. Mutants of the rel+ locus have been isolated (1, 2) and are referred to as "relaxed." Phenotypically, a mutation in the ret locus uncouples the stringent response; i.e., it permits RNA synthesis to continue in the absence of protein synthesis. Similarly, when antibiotics that are known to block protein synthesis at the level of the ribosome are added to a stringent strain, RNA synthesis is uncoupled from protein synthesis. It has been suggested that this latter response is dependent upon the accumulation of charged tRNA whose use in protein synthesis has been spared by the presence of the antibiotic (3). Consequently, it was suggested that for RNA synthesis to occur in a stringent strain, a full complement of charged tRNAs and N-formylmethionyl-tRNA (4, 5) are required.More recently, Cashel and Gallant (6-8) identified two unusual guanosine nucleotides, guanosine tetraphosphate and guanosine pentaphosphate (MSI and MSII, respectively), that accumulate during the inhibition of protein synthesis in a stringent strain, but not in a relaxed strain. It was suggested (8) that accumulated ppGpp and/or ppGppp inhibit(s) stable RNA synthesis. Recently, it was reported that ppGpp inhibits the initiation of rRNA synthesis in vitro (9).The question then remains: is it possible to separate the antiobiotic-induced accumulation of charged tRNA from the synthesis of stable RNA in trivo? If such a distinction can be made, it will be possible to determine the relationship between the relaxed phenotype and the antibiotic-induced accumulation of stable RNA. In this communication, we report that tetracycline is unique among several antibiotics tested in that it can stimulate stable RNA synthesis in a stringent strain of E. coli in the complete absence of either charged valyl-or glutamyltRNA; thus, tetracycline presumably can stimulate RNA synthesis in the absence of any charged tRNA species. Thus, tetracycline seems to have a basic similarity to the rel gene product with respect to its mode of action in the absence of charged tRNA. We also show that in the presence ...

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Section: Discussionmentioning

confidence: 99%

Section: Synthesis Of Ppgpp and Gtpmentioning

confidence: 99%

mentioning

confidence: 99%

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Synthesis of Stable RNA in Stringent Escherichia coli Cells in the Absence of Charged Transfer RNA

Kaplan

Atherly

Barrett

1973

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

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“…In contrast to these immediate consequences for ribosome synthesis, the adjustment of DNA synthesis and cell volume happened more gradually. Removal of required amino acids from auxotrophic mutants of the model bacteria represented an alternative and very informative shift-down, which eventually led to a detailed understanding of the regulation of ribosome synthesis known as the stringent control (Stent and Brenner, 1961;Cashel and Gallant, 1969;Haseltine and Block, 1973). In this control system, the level of uncharged tRNA in the cell plays a key role in de®ning the metabolic state of the cell, with direct consequences for the level of ribosome synthesis.…”

mentioning

confidence: 99%

Application of molecular tools for in situ monitoring of bacterial growth activity

Molin

Givskov

1999

Environmental Microbiology

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“…Nucleotides were determined according to Cashel et al [9,10] by thin-layer chromatography on polyethyleneimine-cellulose of the material soluble in 1 M cold formic acid were performed. The solvent was either 0.8 M or 1.5 M KH2PO4, 2.5.…”

Section: Determination Of the Nucleotide Poolmentioning

confidence: 99%

Effects of 9‐hydroxyellipticine on growth and macromolecular synthesis in Escherichia coli

1976

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Two Compounds implicated in the Function of the RC Gene of Escherichia coli

Cited by 736 publications

References 19 publications

Synthesis of Stable RNA in Stringent Escherichia coli Cells in the Absence of Charged Transfer RNA

Synthesis of Stable RNA in Stringent Escherichia coli Cells in the Absence of Charged Transfer RNA

Application of molecular tools for in situ monitoring of bacterial growth activity

Effects of 9‐hydroxyellipticine on growth and macromolecular synthesis in Escherichia coli

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