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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The stringent factor from Escherichia coli is the product of the relA locus. It is the enzyme that catalyzes the synthesis of pppGpp and ppGpp eliciting a pyrophosphate transfer from ATP to the 3'--OH of GTP (or GDP). This protein is responsible for the synthesis of pppGpp and ppGpp in stringent strains in response to an amino acid starvation. In vitro it catalyzes the synthesis of these guanosine compounds in either a ribosome-dependent reaction that requires a particular conformation of the ribosome i.e. the presence of an uncharged tRNA recognizing a codon in the acceptor (A) site of the ribosome or in a ribosome-independent reaction at temperatures under 30 degrees in the presence of only buffer, salts, and substrates. Here we report the purification of the stringent factor to near homogeneity. It is a monomeric protein with a molecular weight of 75,000. The properties of the ribosome-independent reaction are studied and it is shown that the presence of certain acidic proteins, such as the 50 S ribosomal proteins L7 and L12 or casein, or 20% methanol or both stimulates the reaction by creating an environment that together with the low temperature further stabilizes the stringent factor.
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PMID:Purification and properties of stringent factor. 16 49

When CHO cells are incubated under conditions of extreme amino acid starvation, effected by withdrawal of an amino acid from the medium together with genetic or chemical interference with the activity of the corresponding aminoacyl-tRNA synthetase, there is a rapid and profound decline in the functional capacity of the protein synthetic machinery. The effect was observed for all amino acids tested including leucine, asparagine, histidine, methionine and glutamine. This decline in protein synthetic potential appears to be due to a progressive permanent inactivation of the specific aminoacyl-tRNA synthetase concerned, as shown by a decline in the amount of cellular, specific aminoacyl-tRNA and a decline in the cell-free enzyme activity, measured after reversal of the starvation conditions. When cells are left for more than several hours under these starvation conditions, they shrink in size, lose viability and eventually disintegrate, with anomalous rapidity. We suggest that the progressive loss of protein synthetic capacity of the cells is the prime cause of these subsequent events. If the starvation conditions are reversed before cell death, regeneration of the protein synthetic potential occurs rapidly but requires protein synthesis itself, implying the existence of strong control mechanisms for cellular aminoacyl-tRNA synthetase activities.
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PMID:Effect of extreme amino acid starvation on the protein synthetic machinery of CHO cells. 24 69

A preliminary investigation was carried out to determine how conditional lethal mutants affected in particular aminoacyl-tRNA synthetases may be used to study the role of tRNA charging levels in protein synthesis. The relationship between rate of protein synthesis and level of histidyl-tRNA in wild-type cultured Chinese hamster ovary cells was determined using the analogue histidinol to inhibit histidyl-tRNA synthetase activity. This response was compared with that obtained using a mutant strain with a defective histidyl-tRNA synthetase that phenotypically shows decreased rates of protein synthesis at reduced concentrations of histidine in the growth medium. The approach used was based on measuring the histidyl-tRNA levels in live cells. The percentage charging was estimated by comparing [14C]histidine incorporated into alkali-labile material in paired samples, one of which was treated with cycloheximide, five minutes before terminating during the incubation, to produce maximal aminoacylation. Wild-type cells under histidinol inhibition exhibited a sensitive, sigmoidal relationship between the level of histidyl-tRNA and the rate of protein synthesis. A decrease in the relative percentage of acylated tRNA (His) from 46% to 35% elicited a large reduction in the rate of protein synthesis from 90% to 30% relative to untreated cells. An unpredicted result was that the relationship between protein synthesis and histidyl-tRNA in the mutant was essentially linear. High acylation values for tRNA (His) were associated with rates of protein synthesis that were not nearly as high as in wild-type cells. These findings suggest that the charging charging levels of tRNA (His) isoacceptors could play a regulatory role in determining the rate of protein synthesis under conditions of histidine starvation in normal cells. The mutant appears to be a potentially useful system for studying the pivotal role of tRNA charging in protein synthesis, assuming that the altered response in the mutant is caused by its altered synthetase.
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PMID:Relationship between histidyl-tRNA level and protein synthesis rate in wild-type and mutant Chinese hamster ovary cells. 25 67

The dependence of protein synthesis on the intracellular content of aminoacylated tRNA has been studied in mouse ascites tumor cells deprived for various amino acids. A remarkable reduction in net protein synthesis has been found only after a drastic decrease in aminoacylation of tRNA. The quantitative correlation of protein synthesis with the degree of aminoacylation suggests that a moderate amino acid starvation primarily influences the rate of elongation at the codon concerned. These results are in contrast to the findings previously reported for HeLa cells. Some crucial steps during the determination of intracellular aminoacyl-tRNA have been investigated. The reliability of the method employed has been discussed on a theoretical basis.
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PMID:Control of protein synthesis in mammalian cells by aminoacylation of transfer ribonucleic acid. 26 Jun 96

Methionine starvation of methionine auxotrophs in the presence of excess branched-chain amino acids results in a partial derepression of the isoleucine and valine enzymes. Reversed-phase chromatography indicated that isoleucine, valine and leucine tRNA were altered during methionine starvation. In addition, the total tRNA isolated from cells under these conditions were undermethylated. The observed derepression may be caused by the inability of methyl-deficient tRNA's to participate adequately in normal regulatory functions.
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PMID:Partial derepression of the isoleucine-valine enzymes during methionine starvation is Salmonella typhimurium. 32 Oct 28

The structures of the major, chromatographically unique phenylalanine and leucine tRNAs produced during leucine starvation of a relaxed control (rel-) mutant of E. coli have been determined. The results demonstrate that the unique species are modification-deficient forms of the major, normally occurring isoacceptor species. The unique tRNAphe differs from the fully modified species at nucleotide positions 16, 37, 39, 47, and 55 from the 5' terminus. The unique species contains uridine (U) in place of dihydrouridine-16 (D16), isopentenyladenosine in place of 2-thiomethyl-N6-(delta2-isopentenyl)adenosine-37, a mixture of U and pseudouridine (psi) in position 39, a mixture of U and 3-(3-carboxypropyl)uridine at position 47, and a mixture of U and psi at position 55. The chromatographically normal isoacceptor from amino acid starved cells is deficient in D16 and psi55, indicating that that species is a mixture of mature and undermodified tRNAs. The unique tRNALeu isoacceptor consists of two subspecies which are undermodified forms of the major, normally occurring isoacceptor, tRNALeuI. Both unique subspecies lack the D and psi residues which occur at positions 16 and 39 from the 5' terminus; one subspecies also lacks D17. Compared with the tRNALeusI from wild-type strains of E. coli B and K12, both tRNALeuI from nonstarved cells and the unique, rel-tRNALeu are deficient in the modified guanosine which normally occurs adjacent to the anticodon and the pseudouridine in the GTpsiC sequence of the psi loop. Both the unique tRNAPhe and the unique tRNALeu lack dihydrouridine residues which occur in the 5' half of the D loop and pseudouridines which occur in the 3' half of the anticodon loop and adjoining stem. Taken together, these findings suggest that the same enzymes are responsible for the formation of these particular modified bases in both tRNAs. The results further suggest that several, perhaps most, of the tRNAs from cells cultured under conditions in which RNA and protein synthesis are uncoupled will be similarly deficient in dihydrouridine and pseudouridine and other minor nucleosides which occur less frequently. Because both modification-deficient rel-tRNAs have dihydrouridine at position 20 and pseudouridine in the psi loop (and at position 41 in the unique tRNALeu), the results support the view that there was multiple D-and psi-forming enzymes in E. coli, some of which may turn over rapidly or are selectively inactivated when protein synthesis is blocked. The results are discussed with a view toward understanding the structural basis for the altered biological activity of the unique tRNAPhe species and the order of events in the posttranscriptional modification of newly synthesized tRNA.
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PMID:Modification-deficient transfer ribonucleic acids from relaxed control Escherichia coli: structures of the major undermodified phenylalanine and leucine transfer RNAs produced during leucine starvation. 32 16

The synthesis of tRNA in yeast is shown to be under separate control to that of rRNA during amino acid and nitrogen starvation. Inhibitors of the elongation and termination steps of protein synthesis were found to stimulate the synthesis of tRNA in starved yeast cells. This effect appeared to be due to the "trickle-charging" of tRNA. Two inhibitors of early steps in the initiation of protein synthesis were found to be unable to stimulate RNA synthesis in starved cells. It is proposed that yeast tRNA synthesis is under autoregulatory control and that the level of tRNA charging and the mRNA-ribosome complex are important components of this control system.
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PMID:The regulation of RNA synthesis in yeast. I: Starvation experiments. 33 Oct 81

Previously, we reported that starvation of Rel Escherichia coli for methionine, but not leucine or histidine, results in chromatographically unique species of aspartyl-specific transfer ribonucleic acid (tRNAAsp) lacking the modified nucleoside Q. The present studies demonstrate that methionine starvation of Rel+ E. coli yields a qualitatively similar, but less pronounced, effect. Furthermore, during recovery from methionine starvation in Rel E. coli, the chromatographic elution pattern of tRNAAsp shifts towards that observed for unstarved cells after 1 h of recovery, and the shift appears complete after 2 h of recovery. This shift is inhibited by rifampin. Incorporation of [2-14C]methionine or [methyl-3H]methionine into growing cells of E. coli does not result in labeling of nucleoside Q. We interpret these findings to indicate that methionine has an indirect role in Q formation and that Q-deficient tRNA can be modified slowly to contain Q but that transcription is required. The chromatographic elution patterns of tRNAAsp from Rel E. coli starved for arginine, lysine, or glutamic acid indicate that these amino acids are not the source of the three- or five-carbon sequences in the modified portion of Q.
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PMID:Role of methionine in the synthesis of nucleoside Q in Escherichia coli transfer ribonucleic acid. 33 22

It has been shown that in bacteria, besides specific regulatory mechanisms, the synthesis of aminoacid biosynthetic enzymes is also controlled by the endogenous aminoacid pool. The latter regulates the intracellular level of ppGpp, a positive effector of RNA messenger transcription. A similar regulatory control exists in yeast but does not appear to involve the same general effector. This was established by the observation that derepression of the enzymes belonging to several aminoacid biosynthetic pathways follows aminoacid starvation or tRNA discharging. We now report the repression of the arginine pathway by the total aminoacid pool. New mutations affecting the repressibility of the arginine enzymes as well as enzymes belonging to other aminoacid biosyntheses, when cells are grown in the presence of an excess of aminoacids, were identified.
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PMID:Concerted repression of the synthesis of the arginine biosynthetic enzymes by aminoacids: a comparison between the regulatory mechanisms controlling aminoacid biosyntheses in bacteria and in yeast. 37 2

The plasmid pMY3, which was constructed so as to express the Su+7 amber suppressor tRNA gene, also relaxes control of stable RNA synthesis in stringent cells. The relaxation is not growth medium or strain-dependent and does not occur in the presence of the vehicle alone. When expression of the effective sequence is diminished, in a lysogen of phi 80d3 ilv+Su+7, the sequence no longer affects RNA synthesis. The relaxation is general, extending to all or almost all tRNA loci, including tRNAs located in the ribosomal spacer regions, and to all ribosomal RNAs. Relaxed plasmid-carrying strains are still able to elevate guanosine tetra- and penta-phosphate levels in response to amino acid starvation, but steady state levels are somewhat diminished. Aminoacyl-tRNA falls to control levels when the plasmid-carrying strain is deprived of amino acid. Therefore, the relaxed strain perceives amino acid starvation, but does not respond normally. These properties define a novel locus which relaxes stringent control.
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PMID:Relaxation of stable RNA synthesis by a plasmid-borne locus. 37 46


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