Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.7.6 (RNA polymerase)
34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. alpha-Amanitin inhibits in vitro the RNA polymerase solubilized from isolated rat liver nuclei. 2. In contrast with previous observations with whole nuclei, the inhibition occurs approximately to the same extent in the presence and in the absence of ammonium sulphate. 3. Evidence is presented that the toxin acts by interacting with the enzyme itself and not with DNA or other components.
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PMID:Inhibition by alpha-amanitin of ribonucleic acid polymerase solubilized from rat liver nuclei. 541 93

1. The conditions affecting the activity of RNA polymerase in isolated rat liver nuclei were studied with Mg(2+) or Mn(2+) as activating ions. 2. The enzyme assayed with Mg(2+) and at low ionic strength is saturated by a lower concentration of nucleotide substrates than if assayed with Mn(2+) at low ionic strength or with either ion at high ionic strength. 3. At low and at high ionic strength the incorporation of AMP is affected in a similar way by variations in the temperature of incubation. Preincubation at 37 degrees impairs the AMP incorporation. 4. Heparin stimulates the RNA polymerase activity in the presence of Mn(2+). 5. Both ammonium sulphate and heparin ;restart' the reaction if added after 15min., the effect being more marked with ammonium sulphate than with heparin, and also more marked in the presence of Mn(2+) than of Mg(2+). 6. alpha-Amanitin abolishes the effect of ammonium sulphate and of heparin.
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PMID:Experimental conditions affecting ribonucleic acid polymerase in isolated rat liver nuclei. Effect of nucleoside triphosphate concentration, temperature, ammonium sulphate and heparin. 582 30

Nuclear involvement of the host cell in Junin virus (JV) replication was studied. alpha-Amanitin was shown to inhibit JV yield, and RNA synthesis in cell nuclei was found to be augmented during the eclipse period. JV infection exerted a selective effect on cellular RNA polymerase activities, when measured in purified infected nuclei. RNA polymerase I was inhibited, but RNA polymerase II was stimulated. These data support the hypothesis that RNA polymerase II is involved in arenavirus replication.
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PMID:Induction of RNA polymerase II activity in Junin virus-infected cells. 617 49

Transcriptional activity of the three human placental lactogen (hPL) genes was compared in vitro and their relation to the hPL RNA species obtained from term placenta was analyzed. We used in vitro transcription system containing the HeLa cell crude extract as the source for RNA polymerase II and initiation factors. Gene fragments of identical length of 0.96 kilobase pair made from hPL1, hPL3, and hPL4 each contained the 5' flanking sequence of 497 base pairs, the first exon, the first intron, and a portion of the second exon. More than 90% transcripts of the hPL1 template were 470 nucleotides long, indicating that transcription was initiated at the proposed cap site. hPL3 and hPL4 genes generated heterogeneous RNA products of about 430, 470, 520, and 680 nucleotides suggesting that multiple start points were recognized for RNA synthesis in vitro. alpha-Amanitin sensitivity of transcription indicated that the DNA-dependent RNA synthesis was carried out by RNA polymerase II. These results show that hPL1, hPL3, and hPL4 genes have functional promoters and multiple initiation sites for transcription. Primer extension analysis of the 5' termini of hPL RNA isolated from term placenta shows that 82-83% of the transcripts are initiated at a region 29 base pairs downstream from a "TATA" sequence. This origin is observed in vitro for the transcript 470 nucleotides long. An additional upstream initiation region (-53) accounts for 8% of transcripts in term placenta and corresponds to the origin for the in vitro transcript of 520 nucleotides. At least three other sites 15, 23, and 39 base pairs downstream from the major cap site are functional in vivo. The initiation site at +40 is utilized preferentially for transcription from hPL3 and hPL4 genes in vitro. We have mapped the different transcription origins on hPL genes.
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PMID:Multiple origins of transcription for the human placental lactogen genes. 620 77

The purpose of this work was to study if the steatogenic effect on the liver of Rifampicin, which is an inhibitor of the RNA polymerases DNA dependent in bacteria, can be prevented by an anabolic steroid: 19 nortestosterone phenylproprionate (19-NTPP) which probably stimulates the RNA polymerase activity in eukariotic cells. 19-NTPP (25 mg/kg/24 h, i.p.) was administered to male and both intact and ovariectomized female rats for 8 days prior to the administration of Rifampicin (400 mg/kg/24 h for 8 days). In male rats, 19-NTPP does not prevent the Rifampicin-induced fatty liver. On the contrary, in female rats, 19-NTPP exerts a partial protective effect in intact as well as in ovariectomized animals. These results show that the protective effect of 19-NTPP against Rifampicin fatty liver is less complete and little specific, comparated to the protective effect obtained against another steatogenic compound in female rats: alpha-Amanitin, which is a potent inhibitor of RNA polymerase II in eukariotic cells. In conclusion, the inhibitor effect of Rifampicin on the hepatic apolipoprotein biosynthesis appears as less specific and more intricate than the comparable effect of alpha-Amanitin.
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PMID:Study of the protective effect of an anabolic steroid, 19-nortestosterone phenylpropionate (19-NTPP) on the fatty liver induced by high doses of rifampicin in the rat. 693 30

Recently, it has been demonstrated that nitrogen mustard-induced N-alkylpurines are excised rapidly from actively transcribing genes, while they persist longer in noncoding regions and in the genome overall. It was suggested that transcriptional activity is implicated as a regulatory element in the efficient removal of lesions. By treating cells or not with the transcription inhibitor alpha-amanitin, we have explored whether ongoing activity of RNA polymerase II was coordinately related to proficient repair of nitrogen mustard-induced alkylation products in the actively transcribed dihydrofolate reductase gene in the Chinese hamster ovary B11 cells. Nuclear run-off transcription analysis verified that alpha-amanitin completely and selectively inhibited transcription by RNA polymerase II. At the drug exposure examined, nitrogen mustard induced DNA damage capable of a complete transcription termination in the RNA polymerase II-transcribed dihydrofolate reductase gene and reduced 28S rDNA transcription by a factor of 7.9. The transcription activity did partially recover following reincubation in drug-free medium; this recovery was about 34 and 76% of ribosomal 28S gene transcripts and dihydrofolate reductase gene transcripts, respectively, after 6 h of repair incubation. alpha-Amanitin significantly inhibited the removal of nitrogen mustard-induced N-alkylpurines in the 5'-half of the essential, constitutively active dihydrofolate reductase gene, while no effect of alpha-amanitin was observed on the lesion removal from a noncoding region 3'-flanking to the gene and from the genome overall. In the actively transcribed gene region, about 77% of N-alkylpurines were removed 21 h following drug exposure of cells not treated with alpha-amanitin and about 47% in 21 h in alpha-amanitin treated cells. The global semiconservative replication seemed unaffected by the alpha-amanitin treatment. From these results we suggest that gene-specific repair of nitrogen mustard-induced N-alkylpurines is dependent on ongoing activity of the transcribing RNA polymerase II. The findings are discussed in terms of the current ideas about the mechanism of preferential DNA repair.
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PMID:Ongoing activity of RNA polymerase II confers preferential repair of nitrogen mustard-induced N-alkylpurines in the hamster dihydrofolate reductase gene. 750 96

Using defined elongation complexes formed on dC-tailed templates with Drosophila RNA polymerase II, we have examined elongation, pyrophosphorolysis, and DmS-II-mediated transcript cleavage and the inhibitory effect of alpha-amanitin on these processes. Analysis of pyrophosphorolysis on soluble or immobilized and templates confirmed that NTPs are liberated instead of dinucleotides that are released during DmS-II-mediated transcript cleavage. 10 microgram/ml alpha-amanitin completely inhibited DmS-II-mediated transcript cleavage but allowed extended pyrophosphorolysis and nucleotide addition to occur. alpha-Amanitin dramatically decreased the Vmax for nucleotide addition but only slightly affected the Km for nucleotides. Although the processes ae mechanistically distinct, both pyrophosphorolysis and DmS-II-mediated transcript cleavage frequently resulted in similar patterns of shortened transcript. Since polymerase molecules encounter similar kinetic barriers during both processes, it is possible that there is a common step in the reverse movement of the polymerase.
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PMID:Action of alpha-amanitin during pyrophosphorolysis and elongation by RNA polymerase II. 764 77

We have investigated the effect of phorbol 12-myristate 13-acetate (PMA) on platelet-derived growth factor (PDGF) B-chain gene transcription as well as on mRNA stability in cultured human mesangial cells. Addition of actinomycin to cells stimulated with PMA decreases steady state levels of PDGF-B chain mRNA analysed by solution hybridization assay. PDGF-B chain gene transcription was also assayed directly by measuring elongation of transcripts in isolated nuclei followed by hybridization of labeled RNA transcripts to a cDNA encoding for PDGF-B chain. Our data show that PMA induces PDGF-B chain gene transcription by approximately 2-fold. alpha-Amanitin, an RNA polymerase II inhibitor, blocked transcription by more than 70%. In addition, we determined the effect of PMA on the halflife of PDGF-B chain mRNA directly by pulse chase method. In human mesangial cells, the PDGF-B chain mRNA exhibited halflife of approximately 105 min. In the presence of PMA, the halflife of PDGF-B chain mRNA was reduced to approximately 72 min. These studies indicate that regulation of PDGF-B chain gene by PMA in human mesangial cells involves a coordinate effort at the level of transcription and mRNA stability.
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PMID:Platelet-derived growth factor B-chain gene expression in mesangial cells: effect of phorbol ester on gene transcription and mRNA stability. 787 95

The 100-fold purified RNA polymerase activity from human placenta is completely dependent upon added DNA. The enzyme is most active at 3 mM Mn(2+) in the presence of 100 mM (NH(4))(2)SO(4). Denatured DNA is a better template than native DNA. alpha-Amanitin completely inhibits the incorporation of 3H-UMP, while rifampicin has no influence upon the enzymatic activity.
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PMID:Solubilized DNA-dependent RNA polymerase from human placenta: A Mn(2+)-dependent enzyme. 1194 6

The role of endogenous regucalcin in the regulation of ribonucleic acid (RNA) synthesis activity in the nucleus of normal and regenerating rat livers was investigated. Nuclear RNA synthesis was measured by the incorporation of [(3)H]-uridine 5'-triphosphate into the nuclear RNA in vitro. The presence of regucalcin (0.25 or 0.5 microM) in the reaction mixture caused a significant decrease in nuclear RNA synthesis of normal rat liver. alpha-Amanitin (10(-8)-10(-6) M), an inhibitor of RNA polymerase II and III, decreased significantly nuclear RNA synthesis activity. The effect of regucalcin (0.25 microM) in decreasing nuclear RNA synthesis activity was not seen in the presence of alpha-amanitin (10(-6) M). The calcium chloride (10 microM)-increased nuclear RNA synthesis activity was significantly suppressed by the addition of regucalcin (0.25 microM). RNA synthesis activity was significantly enhanced in the nuclei of regenating rat liver obtained at 24, 48, or 72 h after partial hepatectomy. This enhancement was significantly inhibited in the presence of PD98059 (10(-5) M), staurosporine (10(-6) M), or vanadate (10(-3) M). Western analysis of the nuclei of regenerating liver obtained at 24, 48, or 72 h after partial hepatectomy showed a significant increase in regucalcin protein as compared with that of sham-operated rats. The presence of anti-regucalcin monoclonal antibody (25 or 50 ng/ml) in the reaction mixture caused a significant increase in nuclear RNA synthesis activity of normal rat liver. This increase was completely blocked by the addition of regucalcin (1.0 microM). The effect of anti-regucalcin monoclonal antibody (50 ng/ml) in increasing nuclear RNA synthesis activity was significantly enhanced in the nuclei of regenerating liver obtained at 24, 48, or 72 h after partial hepatectomy. This enhancement was significantly suppressed by the addition of alpha-amanitin (10(-6) M), PD98059 (10(-5) M), staurosporine (10(-6) M), or vanadate (10(-3) M) in the reaction mixture. The present study demonstrates that endogenous regucalcin has a suppressive effect on the enhancement of RNA synthesis activity in the nucleus of regenerating rat liver with proliferative cells.
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PMID:Role of endogenous regucalcin in nuclear regulation of regenerating rat liver: suppression of the enhanced ribonucleic acid synthesis activity. 1239 4


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