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)

A mixture of chemicals was previously devised (3, 3', 5'-triiodo-L-thyronine, amino acids, a butyryl derivative of cyclic adenosine 3':5'-monophosphate, theophylline, and heparin) that induces nuclear DNA replication in the liver of the unoperated rat (Short, J., Tsukada, K., Rudert, W.A. 7 Lieberman, I. (1975) J. Biol. Chem. 250, 3602-3606). The stimulation of DNA synthesis with the complete solution is greater than the sum of the responses to the thyroid hormone alone and to a mixture of the remaining components of the inductive solution alone. The effects of the complete mixture and of parts of it on three parameters involving the hepatocyte nucleolus have now been examined in intact animals. The complete solution increases the level of RNA polymerase I (measured with isolated nuclei), the rate of ribosome synthesis, and the total volume of nucleoli per nucleus. Nucleolar hypertrophy is unique among the three changes in showing a requirement, just as for DNA synthesis, for all or almost all of the components of the complete mixture, including the thyroid hormone, for a maximal effect. Enlargement of nucleoli is detectable as early as 2 hours after the start of treatment with the complete mixture and a large proportion of the total hepatocyte population is involved. Hypertrophy is accompanied by an increase in nucleolar RNA content. N2-Monobutyryl cyclic guanosine 3':5'-monophosphate is not able to substitute for the cyclic adenine nucleotide.
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PMID:Nucleolar changes in liver before the onset of deoxyribonucleic acid replication. 16 95

1. In order to demonstrate that triiodothyronine affects mitochondrial RNA synthesis by acting on the enzyme component of the DNA. RNA polymerase complex, mitochondrial RNA polymerase from thyroidectomized and hormone-treated rats was purified up to a stage in which activity was dependent on the addition of exogenous template. In these conditions and using different DNAs as templates, the enzyme from hormone-treated animals displayed an activity about double that of the activity of thyroidectomized animals. 2. Measurements of stability of mitochondrial RNA synthesized in vitro suggest, however, that the hormone can act also at the template level in mitochondrial transcription: the RNA population synthesized in vitro from hormone-treated rats is indeed much more enriched in unstable, probably messenger, RNA species. 3. The turnover of mitochondrial messenger RNA is higher after hormone treatment. 4. Adenosine cyclic 3':5'-monophosphate (cAMP) and its dibutyryl derivative added in vitro to mitochondria from thyroidectomized animals do not affect the incorporation of labeled precursor into mitochondrial RNA, suggesting that the level of the cyclic nucleotide in mitochondria is probably not involved in the hormone action. 5. It is concluded from these and previous studies that the thyroid hormone affects more than one parameter in the mitochondrial transcription process. The interrelationship between these events at molecular level remains, however, to be clarified.
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PMID:Effects of triiodothyronine on rat-liver mitochondrial transcription process. 16 68

Chromatin receptor proteins appear to mediate some actions of thyroid hormone. In this study, sheared mammalian chromatin containing [125I]triiodothyronine (T3) bound by these receptors was separated using sucrose gradient velocity sedimentation. T3-receptor complexes were distributed throughout the chromatin fractions, but were enriched in the slowly sedimenting fractions. The latter contain most of the template capacity for RNA synthesis and most of the endogenous RNA polymerase activity but a minor portion of the total DNA. Formaldehyde treatment of chromatin containing receptor-bound [125 I ]T3 resulted in fixation of radioactivity, as evidenced by its migration with chromatin after equilibrium density gradient sedimentation in both cesium chloride and Conray. This fixation implies that the T3 receptor protein is closely associated with chromatin. These results suggest that proteins involved in the regulation of gene function may be nonrandomly distributed within chromatin subfractions, and are consistent with a direct role for thyroid hormone in regulating genetic expression.
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PMID:Nuclear receptors for thyroid hormone: evidence for nonrandom distribution within chromatin. 16 76

Synthesis of malic enzyme was rapidly and markedly stimulated by the addition of triiodothyronine to chick embryo liver cells in culture. Alpha-Amanitin, an inhibitor of DNA-dependent RNA polymerase II, blocked induction. The kinetics of induction and de-induction of malic enzyme synthesis suggested that the most stable event in triiodothyronine induction had a half-life of 18 to 20 h. However, malic enzyme synthesis decayed with a half-life of 2,4 h when transcription was inhibited with alpha-amanitin. Thus a long-lived event in thyroid hormone stimulation of malic enzyme synthesis occurred prior to transcription of a specific messenger RNA (mRNA), presumably malic enzyme mRNA. Malic enzyme synthesis decayed with a half-life of about 2 h when glucagon was added to pre-induced liver cells. The similarity of decay rates after inhibition of transcription with alpha-amanitin or inhibition of malic enzyme synthesis by glucagon suggests that glucagon may inhibit the transcription or processing of a specific mRNA required for malic enzyme synthesis.
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PMID:Regulation of malic enzyme synthesis by thyroid hormone and glucagon: inhibitor and kinetic experiments. 56 41

By deletion-transfection analysis, a region of the rat growth hormone gene has been identified which directs accurate, thyroid hormone responsive transcriptional initiation in vivo. In addition, a thyroid hormone-responsive DNase I hypersensitive domain containing three discrete hypersensitive sites has been identified near the GH promoter. One site is coincident with the TATA homology, and the others lie approximately 150 nucleotides 5' and 3' of this sequence. The TATA and 5' flanking DNA hypersensitive sites are located in the region of the gene which promotes hormone-responsive gene transcription. Based on these results, it is possible that the molecular basis for thyroid hormone induction of GH gene transcription includes binding of the occupied receptor to chromatin sites flanking the TATA homology, promoting binding of the TATA activating protein to this sequence. Together, these events may enhance the rate of RNA polymerase II initiation at the promoter.
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PMID:Thyroid hormone transcriptional regulatory region of the growth hormone gene. 269 51

This report summarizes our studies, in context with the results of other laboratories, of the molecular mechanisms of glucocorticoid hormone action. The receptors for these steroids are comprised of single polypeptide chains of about 90,000 molecular weight. Binding of agonist steroids to the receptor induces a conformational change to an active receptor form that is followed by a second change in the glucocorticoid-receptor complex, termed activation, that alters the charge of the complex and results in its binding to specific sites on the DNA termed glucocorticoid regulatory elements (GREs). The GRE on the human metallothionein-IIA gene is located in the 5'-flanking DNA. It can function independently of the gene's promoter, and when ligated upstream from the herpes simplex virus (HSV) thymidine kinase (TK) gene promoter, can activate it. The binding of the glucocorticoid-receptor complex to the GRE probably alters chromatin structure over a limited span to facilitate RNA polymerase action. The regulation by glucocorticoids of growth hormone gene expression is more complex. The steroid appears to elicit both transcriptional and posttranscriptional influences that are also affected by thyroid hormone. Also the glucocorticoid influences appear to be exerted in part through DNA structures located downstream from the transcriptional initiation site. A GRE has been defined in intron A of the hGH gene through gene transfer and DNA binding experiments. Finally, gene transfer experiments suggest that pituitary-specific factors influence the ability of glucocorticoids to affect GH gene expression.
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PMID:Mechanisms of glucocorticoid hormone action. 301 84

In the 'template-engaged' form activity of RNA polymerase I in nuclei of normal rat livers, about 40% of the activity was found to be influenced by thyroid hormones and glucocorticoids and can be eliminated by 1 h treatment with cycloheximide. On the other hand, the 'free' form activity of the enzyme in rat liver nuclei and the total amount of the enzyme in nucleoli were scarcely affected by these hormones. These results suggest that a considerable portion of rRNA synthesis in rat liver nucleoli is regulated by the initiation of rDNA transcription, probably with the participation of glucocorticoid- and thyroid hormone-dependent short-lived protein(s). When somatotropin, in addition to glucocorticoids and thyroid hormones, was depleted by hypophysectomy, the 'template-engaged' form activity of RNA polymerase I was reduced to 30% of the normal level. The activity was restored completely by a single injection of triiodothyronine plus somatotropin, but not by injections of the individual hormones. From these results, it is likely that the stimulating effects of glucocorticoids and thyroid hormones on rRNA synthesis are maintained by the action of somatotropin which seems to occur in a different mechanism from those of the former two hormones. In contrast to these hormones, androgen showed no acute effect on 'template-engaged' form activity of RNA polymerase I in liver nuclei.
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PMID:In vivo effects of thyroid hormone, glucocorticoid, androgen, and somatotropin on RNA polymerase I activities in isolated liver nuclei. 322 49

Our previous study demonstrated that a high level of nuclear triiodothyronine receptors (NT3R), which are identical to the hepatic NT3R, exists in neuronal nuclei of the cerebral cortex from an adult rat brain. To investigate whether thyroid hormone acts through binding to nuclear receptors, we measured RNA polymerase activities in isolated neuronal and glial nuclei of cerebral cortices prepared from three groups of rats with different T3 levels: T3 (20 micrograms/100 g BW/d, for three days)-injected hyperthyroid rats, control normal rats, and thyroidectomized rats. The enzyme activities in both nuclear fractions were assayed under the condition of dose-response linearity. When RNA polymerase I activity in neuronal nuclei from control rats was expressed as 100%, the activities from T3-injected and hypothyroid rats were 112.3 +/- 3.4% (n = 5, P less than .05) and 86.9 +/- 3.5% (n = 5, P less than .05), respectively. The increase in the enzyme activities were parallel to the increase in T3 content in neuronal nuclei among the groups. Glial nuclear RNA polymerase I showed the same tendency in response to T3, although the enzyme activity was smaller than from neuronal nuclei. RNA polymerase II, however, showed no significant change in response to altered T3 levels. The existence of numerous receptors and an induction of increased RNA polymerase I activity by T3 in neuronal nuclei raise the possibility that thyroid hormone through a NT3R pathway in the cerebral cortex of even the mature rat brain.
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PMID:Triiodothyronine effects on RNA polymerase activities in isolated neuronal and glial nuclei of the mature rat brain cortex. 365 13

1. The stimulations of DNA-dependent RNA polymerase in isolated rat-liver nuclei by thyroid hormone, human growth hormone and testosterone are compared. 2. Single or multiple administrations of growth-promoting doses of tri-iodo-l-thyronine, human growth hormone and testosterone stimulate the Mg(2+)-activated RNA-polymerase reaction in nuclei from thyroidectomized, hypophysectomized and castrated rats respectively. The magnitude of stimulation was proportional to the degree of enhancement of liver growth by each hormone. After a single injection, the latent period preceding the stimulation was 1, 2 and 10hr. for growth hormone, testosterone and tri-iodothyronine respectively. The time-course of stimulation of enzyme activity and the synthesis of rapidly labelled nuclear RNA in vivo were also different for each hormone. 3. Growth hormone administration failed to stimulate the Mn(2+)/ammonium sulphate-activated RNA-polymerase reaction. Thyroid hormone and testosterone, however, stimulated it but the effect was less pronounced and occurred several hours later than that observed for the Mg(2+)-activated RNA-polymerase reaction. 4. In combination experiments, hypophysectomized or the thyroidectomized rats were given growth hormone or tri-iodothyronine in a single or repeated doses at levels that produced the maximum stimulation of Mg(2+)-activated RNA-polymerase activity. Taking into account the different latent period for each hormone, a single administration of the second hormone caused an additional stimulation of the enzyme activity. Similar additive effects were observed in thyroidectomized-castrated rats after treatment with tri-iodothyronine and testosterone. The magnitude of the additional stimulation caused by the administration of the second hormone was compatible with the capacity of that hormone to promote liver growth in rats deprived of it. 5. It is concluded that, although these hormones have some similar effects, the regulation of nuclear RNA synthesis may be mediated via different routes for each hormone.
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PMID:Additive effects of thyroid hormone, growth hormone and testosterone on deoxyribonucleic acid-dependent ribonucleic acid polymerase in rat-liver nuclei. 594 53

1. The effect on RNA synthesis in rat liver of thyroidectomy and the administration of thyroid hormone, especially during its physiological latent period, was studied by determining: (a) the activity of DNA-dependent RNA polymerase in isolated nuclei; (b) the rate of synthesis of nuclear and cytoplasmic RNA in vivo; (c) polyribosomal sedimentation profiles; (d) the response of microsomes and ribonucleoprotein particles to polyuridylic acid; (e) the effect of inhibitors of RNA and protein synthesis on the biological activity of hormones. 2. The DNA-dependent RNA-polymerase activity of isolated rat-liver nuclei was lowered by thyroidectomy and stimulated by the administration of tri-iodo-l-thyronine or l-thyroxine (2-25mug./100g. body wt.) to both normal and thyroidectomized rats. In thyroidectomized rats, the activity of the Mg(2+)-activated RNA-polymerase reaction (for which the product is mainly ribosomal type of RNA) was stimulated at 10-12hr. after a single injection of tri-iodothyronine, reaching a peak value of 60-90% stimulation at 45hr. after hormone administration. The Mn(2+)/ammonium sulphate-activated RNA-polymerase reaction (for which the RNA product is more DNA-like) was not affected for 24hr. after hormone administration but stimulated by 30-40% at 45hr. The response of both RNA-polymerase reactions to the hormone in vivo paralleled the physiological response but the enzyme was not stimulated by the addition in vitro of the hormone to isolated nuclei. 3. Within 3-4hr. after tri-iodothyronine administration to thyroidectomized rats, the specific activity of rapidly labelled nuclear RNA, after a 10min. pulse of [6-(14)C]orotic acid, was 30-40% greater than the control values, the stimulation reaching 100 and 200% at 11 and 16hr. respectively after hormone administration. Longer exposures to [6-(14)C]orotic acid and [(32)P]phosphate showed that the hormone accelerated the synthesis of mitochondrial, microsomal (or ribosomal) and soluble RNA. The greater part of the labelled nuclear RNA was of the ribosomal type. The hormone-induced increases in the incorporation of radioactive precursors into RNA were not preceded, but followed, by enhanced uptake of the precursor. There was no change, per g. of liver, of DNA, nuclear RNA or soluble RNA, but there was a 40-60% increase in the amount of ribosomal RNA between 35 and 45hr. after a single injection of tri-iodothyronine to thyroidectomized rats. 4. Coinciding with the increase in ribosomal RNA after hormone administration was an increase in the average size and amount of polyribosomes. The newly formed ribonucleoprotein particles, or messenger RNA attached to them, or both, were more firmly bound to microsomal membranes after hormone treatment. 5. Polyuridylic acid caused a bigger stimulation of incorporation of [(14)C]phenyl-alanine by ribonucleoprotein particles, but not by microsomes, from thyroidectomized rats as compared with preparations from normal animals. The response of ribonucleoprotein particles to polyuridylic acid was lowered after tri-iodothyronine treatment of thyroidectomized rats. 6. Actinomycin D, 5-fluorouracil, puromycin and cycloheximide caused a 70-100% inhibition of the stimulatory effect of l-thyroxine and tri-iodo-l-thyronine on basal metabolic rate and growth rate in both normal and thyroidectomized animals. Administration of actinomycin D also abolished the stimulation of RNA polymerase by tri-iodothyronine. 7. It is concluded that regulation of nuclear and ribosomal RNA synthesis is an essential step leading to the biological action of thyroid hormones and that the formation of new ribosomes is an important aspect of the control of cytoplasmic protein synthesis by these hormones.
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PMID:Ribonucleic acid synthesis during the early action of thyroid hormones. 594 52


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