scholarly journals THE REGULATION OF RNA SYNTHESIS AND PROCESSING IN THE NUCLEOLUS DURING INHIBITION OF PROTEIN SYNTHESIS

1969 ◽  
Vol 41 (1) ◽  
pp. 177-187 ◽  
Author(s):  
Margherita Willems ◽  
Maria Penman ◽  
Sheldon Penman
Keyword(s):  
Protein Synthesis ◽  
Rna Synthesis ◽  
Synthesis Rate ◽  
Protein Synthesis Inhibitor ◽  
Partial Recovery ◽  
Protein Synthesis Inhibition ◽  
Synthesis Inhibitor ◽  
Synthesis Inhibition ◽  
Synthesis And Processing ◽  
Time Required

The effect of protein synthesis inhibition by cycloheximide on nucleolar RNA synthesis and processing has been studied in HeLa cells. Synthesis of 45S RNA precursor falls rapidly after administration of the drug. However, the nucleolar content of 45S RNA remains relatively constant for at least 1 hr because the time required for cleavage of the precursor molecule into its products is lengthened after treatment with cycloheximide. The efficiency of transformation of 45S RNA to 32S RNA remains constant with approximately one molecule of the 32S RNA produced for each cleavage of a molecule of 45S RNA. However, shortly after the cessation of protein synthesis the formation of 18S RNA becomes abortive. The amount of 32S RNA present in the nucleolus remains relatively constant. After long periods of protein synthesis inhibition the 28S RNA continues to be synthesized and exported to the cytoplasm but at a greatly reduced rate. When the protein synthesis inhibitor is removed, a prompt, although partial, recovery in the synthesis rate of 45S RNA occurs. The various aspects of RNA synthesis regulation and processing are discussed.

Regulation of human histone gene expression during the HeLa cell cycle requires protein synthesis

1984 ◽  
Vol 4 (12) ◽  
pp. 2723-2734
Author(s):  
H L Sive ◽  
N Heintz ◽  
R G Roeder
Keyword(s):  
Cell Cycle ◽  
Protein Synthesis ◽  
S Phase ◽  
Histone Gene ◽  
Protein Synthesis Inhibitor ◽  
Protein Synthesis Inhibition ◽  
Synthesis Inhibitor ◽  
Synthesis Inhibition ◽  
Histone Mrnas ◽  
Histone Gene Expression

We have examined the effects of protein synthesis inhibition on histone gene expression during the HeLa cell cycle. Histone mRNAs, which normally are rapidly degraded in the absence of DNA synthesis, persist and increase in concentration when translation is inhibited before DNA replication is halted. This is not a function of polysomal shielding of these mRNAs from active degradation mechanisms since inhibitors of translation initiation alone effect stabilization and induction. The superinduction of histone mRNAs by protein synthesis inhibition is effective at the G1/S border, and in the S-phase and non-S-phase periods of the cell cycle. However, the relative increase in histone mRNA is greater when cells not synthesizing DNA are treated with a protein synthesis inhibitor than when S-phase cells are so treated. Non-histone mRNAs examined are not superinduced by translation inhibition. Transcription rates from both histone and non-histone genes increase after protein synthesis inhibition. Although the decrease in histone gene transcription associated with DNA synthesis inhibition is prevented and reversed by protein synthesis inhibition, we have no evidence that histone gene-specific transcriptional regulation is dependent on protein synthesis. Transcriptional increases may contribute to the superinduction effect but cannot explain its differential extent during the cell cycle, since these increases are similar when replicating or nonreplicating cells are treated with a protein synthesis inhibitor. We believe that changes in histone mRNA stability can account for much of the differential superinduction effect. Our results indicate a requirement for continuing protein synthesis in the cell cycle regulation of histone mRNAs.

Effect of protein synthesis Inhibition on brain corticotropin-releasing factor and plasma adrenocorticotropin

1990 ◽  
Vol 68 (12) ◽  
pp. 1595-1600
Author(s):  
Daniel A. Haas ◽  
William C. Sturtridge ◽  
Susan R. George
Keyword(s):  
Protein Synthesis ◽  
Corticotropin Releasing Factor ◽  
Protein Synthesis Inhibitor ◽  
Protein Synthesis Inhibition ◽  
Plasma Acth ◽  
Synthesis Inhibitor ◽  
Brain Areas ◽  
Synthesis Inhibition ◽  
General Protein Synthesis ◽  
General Protein

The effect of inhibiting protein synthesis on concentrations of corticotropin-releasing factor (CRF) in rat brain and plasma adrenocorticotropin (ACTH) was assessed following the administration of the general protein synthesis inhibitor anisomycin. Compared with vehicle-injected controls, protein synthesis inhibition resulted in significantly reduced CRF immunoreactivity (CRF-ir) in median eminence within 1 h (p < 0.01), remained decreased after 4 h (p < 0.025), and was nonsignificantly decreased after 24 h. Plasma ACTH levels were greatly increased within 1 h posttreatment (p < 0.0005), continued elevated after 4 h (p < 0.01), and returned to normal levels after 24 h. CRF-ir measured in other brain areas 24 h after anisomycin showed decreased levels in medulla–pons (p < 0.025) and neurointermediate lobe of pituitary (p < 0.05), with no change noted in frontal cortex, hippocampus, midbrain–thalamus, or cerebellum. Overall these data show that blockade of normal protein synthesis with anisomycin can elicit changes in CRF-ir and ACTH content.Key words: corticotropin-releasing factor, adrenocorticotropin, anisomycin.

scholarly journals Regulation of human histone gene expression during the HeLa cell cycle requires protein synthesis.

1984 ◽  
Vol 4 (12) ◽  
pp. 2723-2734 ◽  
Author(s):  
H L Sive ◽  
N Heintz ◽  
R G Roeder
Keyword(s):  
Cell Cycle ◽  
Protein Synthesis ◽  
S Phase ◽  
Histone Gene ◽  
Protein Synthesis Inhibitor ◽  
Protein Synthesis Inhibition ◽  
Synthesis Inhibitor ◽  
Synthesis Inhibition ◽  
Histone Mrnas ◽  
Histone Gene Expression

We have examined the effects of protein synthesis inhibition on histone gene expression during the HeLa cell cycle. Histone mRNAs, which normally are rapidly degraded in the absence of DNA synthesis, persist and increase in concentration when translation is inhibited before DNA replication is halted. This is not a function of polysomal shielding of these mRNAs from active degradation mechanisms since inhibitors of translation initiation alone effect stabilization and induction. The superinduction of histone mRNAs by protein synthesis inhibition is effective at the G1/S border, and in the S-phase and non-S-phase periods of the cell cycle. However, the relative increase in histone mRNA is greater when cells not synthesizing DNA are treated with a protein synthesis inhibitor than when S-phase cells are so treated. Non-histone mRNAs examined are not superinduced by translation inhibition. Transcription rates from both histone and non-histone genes increase after protein synthesis inhibition. Although the decrease in histone gene transcription associated with DNA synthesis inhibition is prevented and reversed by protein synthesis inhibition, we have no evidence that histone gene-specific transcriptional regulation is dependent on protein synthesis. Transcriptional increases may contribute to the superinduction effect but cannot explain its differential extent during the cell cycle, since these increases are similar when replicating or nonreplicating cells are treated with a protein synthesis inhibitor. We believe that changes in histone mRNA stability can account for much of the differential superinduction effect. Our results indicate a requirement for continuing protein synthesis in the cell cycle regulation of histone mRNAs.

scholarly journals ON THE MECHANISM OF ADAPTATION TO PROTEIN SYNTHESIS INHIBITORS BY TETRAHYMENA

1974 ◽  
Vol 62 (3) ◽  
pp. 707-716 ◽  
Author(s):  
Charles T. Roberts ◽  
Eduardo Orias
Keyword(s):  
Protein Synthesis ◽  
Cell Division ◽  
Protein Synthesis Inhibitor ◽  
Protein Synthesis Inhibitors ◽  
Cellular Functions ◽  
Synthesis Inhibitor ◽  
Experimental Conditions ◽  
Cellular Machinery ◽  
Time Required ◽  
Sublethal Concentrations

Tetrahymena is able to adapt to the presence of sublethal concentrations of many drugs which inhibit a wide variety of cellular functions. In spite of the generality of this phenomenon in Tetrahymena, the mechanism of adaptation at the cellular and molecular levels is unknown. This study deals mainly with adaptation to the protein synthesis inhibitors, cycloheximide and emetine. The physiological response of Tetrahymena to sublethal concentrations of these drugs is an immediate cessation of cell division for a period of time dependent on the drug concentration, followed by an abrupt resumption of exponential growth at a constant rate. By measuring the length of the growth lags under a variety of experimental conditions, we have confirmed several observations made by Frankel and coworkers, and provide evidence for two new phenomena associated with adaptation to cycloheximide: (a) adaptation to cycloheximide also results in adaptation of cells to emetine, another protein synthesis inhibitor not closely related structurally to cycloheximide. We have termed this phenomenon cross adaptation, (b) exposure to concentrations of cycloheximide too low to cause any growth lags or inhibition of protein synthesis significantly shortens the time required by cells to adapt to higher concentrations of cycloheximide. We have termed this phenomenon facilitation. Facilitation shows some degree of specificity in that facilitation with cycloheximide has no effect on adaptation to emetine. From this, we infer the existence of two distinct systems involved in adaptation to cycloheximide, one of which shows a higher degree of specificity towards cycloheximide than the other. We also show that transfer of adapted or facilitated cells to drug-free medium results in a gradual but complete resensitization. The kinetics of resensitization suggest that the cellular machinery responsible for adaptation and facilitation does not leave the cell, but is simply diluted out during cell division.

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