scholarly journals THE EFFECT OF PUROMYCIN ON INTRANUCLEAR STEPS IN RIBOSOME BIOSYNTHESIS

1968 ◽  
Vol 36 (1) ◽  
pp. 91-101 ◽  
Author(s):  
R. Soeiro ◽  
M. H. Vaughan ◽  
J. E. Darnell
Keyword(s):  
Protein Synthesis ◽  
Ribosomal Rna ◽  
Cell Fractionation ◽  
Sequence Of Events ◽  
Inhibition Of Protein Synthesis ◽  
Precursor Rna ◽  
Initial Processing ◽  
Inhibitor Of Protein Synthesis ◽  
Ribosomal Precursor ◽  
Ribosome Biosynthesis

Inhibition of protein synthesis by puromycin (100 γ/ml) is known to inhibit the synthesis of ribosomes. However, ribosomal precursor RNA (45S) continues to be synthesized, methylated, and processed. Cell fractionation studies revealed that, although the initial processing (45S → 32S + 16S) occurs in the presence of puromycin, the 16S moiety is immediately degraded. No species of ribosomal RNA can be found to have emerged from the nucleolus. The RNA formed in the presence of puromycin is normal as judged by its ability to enter new ribosomal particles after puromycin is removed. This sequence of events is not a result of inhibition of protein synthesis, for cycloheximide, another inhibitor of protein synthesis, either alone or in combination with puromycin allows the completion of new ribosomes.

scholarly journals Carcinogenesis and Cellular Injury. The effect of ethionine on ribonucleic acid synthesis in rat liver

1975 ◽  
Vol 150 (3) ◽  
pp. 335-344 ◽  
Author(s):  
P F Swann ◽  
A C Peacock ◽  
S Bunting
Keyword(s):  
Protein Synthesis ◽  
Rna Synthesis ◽  
Acid Synthesis ◽  
Female Rat ◽  
Concurrent Administration ◽  
Polyamine Synthesis ◽  
Rrna Maturation ◽  
Precursor Rna ◽  
Inhibitor Of Protein Synthesis ◽  
Ribosomal Precursor

1. By 1h after administration of ethionine to the female rat the appearance of newly synthesized 18SrRNA in the cytoplasm is completely inhibited. This is not caused by inhibition of RNA synthesis, for the synthesis of the large ribosomal precursor RNA (45S) and of tRNA continues. Cleavage of 45S RNA to 32S RNA also occurs, but there was no evidence for the accumulation of mature or immature rRNA in the nucleus. 2. The effect of ethionine on the maturation of rRNA was not mimicked by an inhibitor of protein synthesis (cycloheximide) or an inhibitor of polyamine synthesis [methylglyoxal bis(guanylhydrazone)]. 3. Unlike the ethionine-induced inhibition of protein synthesis, this effect was not prevented by concurrent administration of inosine. A similar effect could be induced in HeLa cells by incubation for 1h in a medium lacking methionine. The ATP concentration in these cells was normal. From these two observations it was concluded that the effect of etionine on rRNA maturation is not caused by an ethionine-induced lack of ATP. It is suggested that ethionine, by lowering the hepatic concentration of S-adenosylmethionine, prevents methylation of the ribosomal precursor. The methylation is essential for the correct maturation of the molecule; without methylation complete degradation occurs.

scholarly journals Inhibition of protein synthesis by an efficiently expressed mutation in the yeast 5.8S ribosomal RNA

1994 ◽  
Vol 22 (4) ◽  
pp. 686-693 ◽  
Author(s):  
Sherif Abou Elela ◽  
Liam Good ◽  
Yuri F. Melekhovets ◽  
Ross N. Nazar
Keyword(s):  
Protein Synthesis ◽  
Ribosomal Rna ◽  
Inhibition Of Protein Synthesis

Activated ribosomal RNA synthesis in regenerated rat liver upon inhibition of protein synthesis

1991 ◽  
Vol 15 (1) ◽  
pp. 45-52 ◽  
Author(s):  
Emil H. Nikolov ◽  
Bistra B. Nankova ◽  
Mariana D. Dabeva
Keyword(s):  
Protein Synthesis ◽  
Rat Liver ◽  
Ribosomal Rna ◽  
Rna Synthesis ◽  
Inhibition Of Protein Synthesis

scholarly journals THE EFFECTS OF INHIBITORS OF RNA AND PROTEIN SYNTHESIS ON THE RECOVERY OF CHLOROPLAST RIBOSOMES, MEMBRANE ORGANIZATION, AND PHOTOSYNTHETIC ELECTRON TRANSPORT IN THE ac-20 STRAIN OF CHLAMYDOMONAS REINHARDI

1971 ◽  
Vol 50 (1) ◽  
pp. 50-62 ◽  
Author(s):  
Ursula W. Goodenough ◽  
R. P. Levine
Keyword(s):  
Protein Synthesis ◽  
Electron Transport ◽  
Chloroplast Dna ◽  
Ribosomal Rna ◽  
Structural Integrity ◽  
Photosynthetic Electron Transport ◽  
Rna And Protein Synthesis ◽  
Low Levels ◽  
Inhibitor Of Protein Synthesis ◽  
Secondary Consequence

The ac-20 strain of Chlamydomonas reinhardi is characterized by low levels of chloroplast ribosomes when grown mixotrophically. Cells can be transferred to minimal medium and their ribosome levels increase. If, at the time of transfer, cells are exposed to chloramphenicol, an inhibitor of protein synthesis in the chloroplast, or cycloheximide, an inhibitor of protein synthesis in the cytoplasm, ribosome recovery is not affected; however, recovery is blocked by exposure to rifampicin, an inhibitor of chloroplast DNA-dependent RNA polymerase. It is therefore concluded that ac-20 cells suffer from an impaired chloroplast ribosomal RNA synthesis. Mixotrophic ac-20 cells are also characterized by low rates of photosynthetic electron transport, disorganized chloroplast membranes, and a small pyrenoid. If chloramphenicol is applied to transferred cells whose chloroplast ribosome levels have already recovered, recovery of photosynthetic electron transport and of structural integrity does not occur. Under the same conditions, cycloheximide has no effect on recovery. It is concluded that the structural and photosynthetic lesions in ac-20 are a secondary consequence of the low levels of chloroplast ribosomes. Finally, we present evidence that recovery of photosynthetic electron transport requires the transcription of chloroplast DNA. This transcription is apparently triggered by light.

scholarly journals NUCLEAR ENVELOPE-ASSOCIATED RESUMPTION OF RNA SYNTHESIS IN LATE MITOSIS OF HELA CELLS

1973 ◽  
Vol 59 (1) ◽  
pp. 150-164 ◽  
Author(s):  
T. Simmons ◽  
P. Heywood ◽  
L. Hodge
Keyword(s):  
Protein Synthesis ◽  
Nuclear Envelope ◽  
Rna Synthesis ◽  
Electron Microscope Autoradiography ◽  
Molecular Synthesis ◽  
Hela S3 ◽  
Precursor Rna ◽  
Ribosomal Precursor ◽  
Hela S3 Cells ◽  
Silver Grains

The restitution of RNA synthesis in cultures progressing from metaphase into interphase (G1) has been investigated in synchronized HeLa S3 cells by using inhibitors of macro-molecular synthesis and the technique of electron microscope autoradiography. The rate of incorporation of radioactive uridine into RNA approached interphase levels in the absence of renewed protein synthesis. In contrast, maintenance of this rate in G1 was dependent upon renewed protein synthesis. Restoration of synthesis of heterogeneous nuclear RNA occurred under conditions that inhibited production of ribosomal precursor RNA. In autoradiographs of individual cells exposed to radioactive uridine, silver grains were first detected after nuclear envelope reformation at the periphery of the chromosome mass but before chromosomal decondensation. These data are consistent with the following interpretation. Multiple RNA polymerase activities persist through mitosis and are involved in the initiation of RNA synthesis in early telophase at sites on the nuclear envelope.

scholarly journals Investigations of the Mode of Action and Resistance Development of Cadazolid, a New Antibiotic for Treatment of Clostridium difficile Infections

2013 ◽  
Vol 58 (2) ◽  
pp. 901-908 ◽  
Author(s):  
Hans H. Locher ◽  
Patrick Caspers ◽  
Thierry Bruyère ◽  
Susanne Schroeder ◽  
Philippe Pfaff ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Clostridium Difficile ◽  
Dna Synthesis ◽  
Mode Of Action ◽  
Cross Resistance ◽  
Resistance Development ◽  
Content Type ◽  
Inhibition Of Protein Synthesis ◽  
Inhibitor Of Protein Synthesis ◽  
Inhibition Of Dna Synthesis

ABSTRACTCadazolid is a new oxazolidinone-type antibiotic currently in clinical development for the treatment ofClostridium difficile-associated diarrhea. Here, we report investigations on the mode of action and the propensity for spontaneous resistance development inC. difficilestrains. Macromolecular labeling experiments indicated that cadazolid acts as a potent inhibitor of protein synthesis, while inhibition of DNA synthesis was also observed, albeit only at substantially higher concentrations of the drug. Strong inhibition of protein synthesis was also obtained in strains resistant to linezolid, in agreement with low MICs against such strains. Inhibition of protein synthesis was confirmed in coupled transcription/translation assays using extracts from differentC. difficilestrains, including strains resistant to linezolid, while inhibitory effects in DNA topoisomerase assays were weak or not detectable under the assay conditions. Spontaneous resistance frequencies of cadazolid were low in all strains tested (generally <10−10at 2× to 4× the MIC), and in multiple-passage experiments (up to 13 passages) MICs did not significantly increase. Furthermore, no cross-resistance was observed, as cadazolid retained potent activity against strains resistant or nonsusceptible to linezolid, fluoroquinolones, and the new antibiotic fidaxomicin. In conclusion, the data presented here indicate that cadazolid acts primarily by inhibition of protein synthesis, with weak inhibition of DNA synthesis as a potential second mode of action, and suggest a low potential for spontaneous resistance development.

scholarly journals Mechanism of action of a microsomal inhibitor of protein synthesis potentiated by oxidized glutathione

1973 ◽  
Vol 136 (2) ◽  
pp. 335-342 ◽  
Author(s):  
H. T. R. Rupniak ◽  
R. V. Quincey
Keyword(s):  
Protein Synthesis ◽  
Mechanism Of Action ◽  
Nucleoside Triphosphate ◽  
Oxidized Glutathione ◽  
Direct Inhibition ◽  
Nucleoside Triphosphate Diphosphohydrolase ◽  
Inhibition Of Protein Synthesis ◽  
Inhibitor Of Protein Synthesis

Extracts of microsomal fractions cause an inhibition of protein synthesis that is most pronounced in the presence of 0.1mm-GSSG and 0.01mm-GTP, and is abolished by thiol or 0.4mm-GTP (Scornik et al., 1967). Fractionation of microsomal extracts showed that this inhibition of protein synthesis was caused by an enzyme, nucleoside diphosphate phosphohydrolase. Direct inhibition of protein synthesis on detergent-treated polyribosomes by 0.1mm-GSSG was observed under conditions of GTP limitation induced by omission of a GTP-regenerating system, or addition of a nucleoside triphosphate diphosphohydrolase. Thus GSSG potentiated the inhibition of protein synthesis caused by an enzyme that promoted removal of GTP. The inhibition was abolished by adding 4mm-2-mercaptoethanol or 0.4mm-GTP. Nucleoside diphosphate phosphohydrolase was thought also to act by promoting removal of GTP, thus causing an inhibition of protein synthesis that was potentiated by GSSG.

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