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

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.

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

The Journal of Cell Biology ◽

10.1083/jcb.41.1.177 ◽

1969 ◽

Vol 41 (1) ◽

pp. 177-187 ◽

Cited By ~ 149

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.

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

Molecular and Cellular Biology ◽

10.1128/mcb.4.12.2723 ◽

1984 ◽

Vol 4 (12) ◽

pp. 2723-2734 ◽

Cited By ~ 35

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.

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Corticotropin-Releasing Factor Produces a Protein Synthesis–Dependent Long-Lasting Potentiation in Dentate Gyrus Neurons

Journal of Neurophysiology ◽

10.1152/jn.2000.83.1.343 ◽

2000 ◽

Vol 83 (1) ◽

pp. 343-349 ◽

Cited By ~ 46

Author(s):

Hai L. Wang ◽

Li Y. Tsai ◽

Eminy H. Y. Lee

Keyword(s):

Protein Synthesis ◽

Synaptic Transmission ◽

Dentate Gyrus ◽

Late Phase ◽

Long Term Potentiation ◽

Corticotropin Releasing Factor ◽

Rat Hippocampus ◽

Protein Synthesis Inhibitor ◽

Synthesis Inhibitor

Corticotropin-releasing factor (CRF) was shown to produce a long-lasting potentiation of synaptic efficacy in dentate gyrus neurons of the rat hippocampus in vivo. This potentiation was shown to share some similarities with tetanization-induced long-term potentiation (LTP). In the present study, we further examined the mechanism underlying CRF-induced long-lasting potentiation in rat hippocampus in vivo. Results indicated that the RNA synthesis inhibitor actinomycin-D, at a concentration that did not change basal synaptic transmission alone (5 μg), significantly decreased CRF-induced potentiation. Similarly, the protein synthesis inhibitor emetine, at a concentration that did not affect hippocampal synaptic transmission alone (5 μg), also markedly inhibited CRF-induced potentiation. These results suggest that like the late phase of LTP, CRF-induced long-lasting potentiation also critically depend on protein synthesis. Further, prior maximum excitation of dentate gyrus neurons with tetanization occluded further potentiation of these neurons produced by CRF and vise versa. Moreover, quantitative reverse transcription-polymerase chain reaction analysis revealed that CRF mRNA level in the dentate gyrus was significantly increased 1 h after LTP recording. Together with our previous findings that CRF antagonist dose-dependently diminishes tetanization-induced LTP, these results suggest that both CRF-induced long-lasting potentiation and tetanization-induced LTP require protein synthesis and that CRF neurons are possibly involved in the neural circuits underlying LTP.

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