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)

Present epidemic influenza is uncontrolled by immuno- or chemoprophylaxis. Mutants of varying antigenic composition arise with relatively high frequency in nature and are able to circumvent herd, or induced, immunity. Also, drug-resistant viruses can be selected in vitro and this resistance can be exchanged to other viruses by gene reassortment. Combined immuno- and chemoprophylaxis may provide a more effective approach to the ultimate control of the disease. Most antiviral compounds have been selected by random screening in the laboratory. Application of more specific enzyme assays such as the virion-associated RNA transcriptase assays may produce other compounds with a defined mode of action - semi-rational chemotherapy. RNA and polypeptide sequence studies are in progress elsewhere to define transcription and translation initiation sites or virus adsorption sites. Such knowledge could lead to a new generation of antiviral compounds. Specific delivery of virus inhibitory compounds is an interesting problem. Liposomes are lipid spheres, and these have been used for the delivery of antiviral compounds.
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PMID:Approaches towards rational antiviral chemotherapy. 46 Dec 75

The constituent polypeptides of the three classes of DNA-dependent RNA polymerase from Acanthamoeba castellanii were compared by several electrophoretic methods. Polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate (SDS) reveals that a number of polypeptide components of the isozymes have identical molecular weights. Two-dimensional electrophoresis (isoelectric focusing in 8 M urea:SDS-polyacrylamide gel electrophoresis) demonstrates that the polypeptides of identical molecular weights also have identical isoelectric pH values. These polypeptides were also coincident after electrophoresis in 8 M urea at acidic or basic pH values followed by a second electrophoretic separation in the presence of SDS. By these criteria, subunits of molecular weight 13,300, 15,500, 17,500, 22,500, 37,000, and 39,000 are indistinguishable in polymerase I and III. The 13,300, 15,500, and 22,500 subunits are also shared by the class II polymerase. In addition, electrophoresis in 8 M urea under basic conditions reveals microheterogeneity in the 17,500 molecular weight subunit. The strikingly similar pattern of common subunits between yeast and Acanthamoeba suggests that a universal arrangement of functional units may be an essential feature of the eukaryotic polymerases.
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PMID:DNA-dependent RNA polymerases from Acanthamoeba castellanii. Comparative subunit structures of the homogeneous enzymes. 50 Jun 45

The earliest stages of mouse embryogenesis, from fertilisation to the two-cell stage, are characterised by an extremely low level of RNA synthesis. Indeed, during this period, RNA polymerase II activity and incorporation of labelled precurosrs into heterogeneous RNA are not detectable, and there is no increase in the poly(A) content of the embryo, but rather a slight decrease. The rate of protein synthesis remains low and relatively constant throughout the one- and two-cell stages. However, qualitative analysis of the protein synthetic profile on SDS gels has revealed changes which appear around the late one-cell to early two-cell stage. This early change in the pattern of polypeptide synthesis represents the first major qualitative molecular change found so far in development. We present evidence which suggests that the increased synthesis at the early two-cell stage of a small number of polypeptides of molecular weight 35,000 is not dependent on transcription, but rather represents control at a post-transcriptional level using mRNAs synthesised before fertilisation.
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PMID:Post-transcriptional control in the early mouse embryo. 50 84

We report the first measurement of the magnetic circular dichroism (MCD) of the basic polypeptide antibiotic netropsin (Nt). The MCD shows that the longest wavelength absorption band of Nt is the sum of more than one component and permits a radically new interpretation of the circular dichroism of the complex which Nt forms with DNA. We conclude that Nt has no major effect on the CD and thus the helical structure of the bases of the DNA to which it is bound. Thus the ability of Nt to inhibit the function of DNA polymerase, RNA polymerase, and the photoreactivating enzyme must be mediated by factors other than a distortion of the helical structure of the bases.
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PMID:Magnetic circular dichroism of netropsin and natural circular dichroism of the netropsin-DNA complex. 56 96

When Semliki Forest virus ts-4 mutant infected cultures are grown at the permissive temperature (28 degrees C) and shifted to the restrictive temperature (39 degrees C), two different defects in RNA synthesis are manifested: (i) the synthesis of 26S RNA is stopped within 60 min (Saraste et al. 1977) and (ii) the increase in RNA synthesizing activity ceases, in contrast to cultures maintained at 28 degrees C, indicating that no new active RNA polymerase is formed at 39 degrees C. Accumulation of a non-structural precursor protein with an apparent mol. wt. of about 220 000 (ns220) was demonstrated in ts-4 infected cultures shifted to 39 degrees C. NS220 was labelled during short pulses given immediately after release of protein synthesis from hypertonic initiation block, suggesting that genes coding for ns220 are located near the initiation site at the 5'-end of the 42S RNA. The viral specificity of ns220 was shown by its disappearance after a shift to 28 degrees C and by labelling in the presence of sucrose, when no host cell protein synthesis is detectable. The two functional defects can be explained if the polypeptides responsible for the RNA polymerizing activity and that responsible for the synthesis of 26S RNA are components of the same non-structural polyprotein. A mutation in the latter polypeptide which prevents cleavage of the polyprotein would thereby prevent the further formation of active RNA polymerase. If cleavage of the polyprotein has taken place at the permissive temperature, the RNA polymerase would remain active also at 39 degrees C, whereas the polypeptide responsible for 26S RNA synthesis would become inactive due to the mutation.
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PMID:Cleavage defect in the non-structural polyprotein of Semliki Forest virus has two separate effects on virus RNA synthesis. 66 Jan 63

The effect of cerebral ischemia on polypeptide synthesis with isolated microsomes and DNA-dependent RNA polymerase activity with isolated nuclei was investigated by occlusion of right common carotid artery of gerbils. There was a prompt decline of microsomal polypeptide synthesis already at 30 min after occlusion of the artery, and at 4--5 h the specific radioactivity (dpm per microgram protein) was 50% of the control value. At 24 h, when the animals were only slightly responsive to external stimuli, the specific radioactivity of ischemic brain was only 20% of the control value. DNA-dependent RNA polymerase activity was unaffected for 1 h, and clear suppression did not appear until 3 h after occlusion. However, the extent of suppression was similar between polypeptide synthesis and RNA polymerase activity beyond 3 h after occlusion. Although more selective vulnerability of polypeptide synthesis thus exists in cerebral ischemia, the difference between two biochemical processes was not as striking as seen in cerebral anoxia. Focal progression of cerebral ischemia to diffuse infarction in gerbils was suggested as a possible explanation for the disparity in comparison to the diffuse effect in cerebral anoxia along with the difference in the magnitude of acidosis and depletion of energy reserve.
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PMID:Experimental stroke in gerbils: effect on translation and transcription. 70 73

The subunits of yeast RNA polymerases A(I) and B(II) were characterized using several techniques. The present studies demonstrate that the A and B enzymes possess three subunits, which are indistinguishable on the basis of molecular weight, isoelectric point, and fingerprint pattern. The three common subunits belong to the small molecular weight components of the enzymes. By polyacrylamide gel electrophoresis with sodium dodecyl sulfate they migrate with apparent molecular weights of 27,000, 23,000, and 14,500, respectively. A two-dimensional subunit mapping technique on polyacrylamide gel was used to separate the subunits according to isoelectric point and molecular weight. The common polypeptides co-migrated on three spots corresponding to isoelectric points of 9.2 (27,000), 4.5 (23,000), and 4.6 (14,500). The fingerprints of the 35S-labeled tryptic peptides of the presumptive common subunits were found to be essentially identical. Finally, the presence of common subunits was supported by the fact that antibodies against pure RNA polymerase A cross-react with and inhibit RNA polymerase B. Except for the common subunits, it is likely that RNA polymerases A and B are primarily made of distinct gene products for the following reasons. A total of 13 polypeptide chains are present in enzyme A, whereas 10 polypeptides are found in enzyme B. The molecular weight, isoelectric point, and sulfur content of the majority of these polypeptide chains are different in the two enzymes. No similarity was found in the 35S-peptide fingerprint from a number of A and B subunits of slightly different molecular weight. Finally, antibodies against the largest subunit from RNA polymerase A do not cross-react with or inhibit RNA polymerase B. The data are discussed in terms of structural organization of eukaryotic RNA polymerases.
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PMID:Structural studies on yeast RNA polymerases. Existence of common subunits in RNA polymerases A(I) and B(II). 76 38

The addition of cycloheximide to a thermosensitive conditional yeast mutant (ts-187) before and after transfer to the nonpermissive temperature (36 degrees C) for initiation of protein synthesis produces the uncoupling of the RNA and protein synthetic machineries. Since the drug can produce this relaxation in the presence and absence of protein synthesis, it is concluded that the coupling of protein and RNA synthesis, which a temperature shift produces, is not exclusively related to the inhibition of protein synthesis. Support for this assumption has been obtained using the parental (A364A) strain. Transferring this strain to 36 degrees C produces inhibition of RNA synthesis in the presence of stimulation of protein synthesis. Furthermore, cycloheximide and edeine prevent this inhibtion of RNA synthesis that temperature shift produces. It is, therefore, postulated that this inhibition of RNA synthesis results from the synthesis or activation of a factor(s) elicited by the increase in temperature whose function is to repress the transcriptional apparatus. Cycloheximide or edeine can prevent the function of this repressor-like factor by binding to the factor or by preventing its synthesis. The fact that inhibition of protein synthesis either by cycloheximide action or temperature shift in ts-187 produces inhibition of RNA synthesis in isolated nuclei indicates that, in addition to the aforementioned repressor, other factor(s) having a promoter function may exist. Since a slight inhibition of protein synthesis produces nuclear template restrictions, it is postulated that the promoter-like factor(s) is a polypeptide different from the RNA polymerase and, at least in yeast, has a high turnover.
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PMID:Control of ribonucleic acid synthesis in eukaryotes. 3. The effect of cycloheximide and edeine on rna synthesis in yeast. 77 14

1. The surface of the RNA-polymerase-DNA complex possesses an exposed polypeptide loop. 2. Proteinases with differing specificities (trypsin, chymotrypsin, subtilisin and clostripain) preferentially cleave the exposed region. 3. The cleaved polypeptide is reassembled into RNA polymerase by renaturation from a solvent which promotes a random coil conformation. 4. Isolated beta subunit has a proteolytically resistant nucleus of approximately 70000 molecular weight. This resistant polypeptide may be generated by trypsin, chymotrypsin, subiilisin or clostripain. 5. Isolated alpha subunits are comparatively resistant to proteolysis. 6. Although of similar molecular weights beta and beta' appear to have unrelated primary sequences and markedly different conformations in free solution. 7. Digestion of the beta subunit may be blocked by formation of the alpha2beta subassembly. 8. Evidence is presented suggesting that beta' in the intact enzyme (alpha2beta beta') possesses the exposed polypeptide loop.
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PMID:Structural properties of Escherichia coli RNA polymerase Subunits. 77 11

Special care to prevent proteolysis during yeast RNA polymerase B purification leads to the appearance of two forms of enzymes, BI and BII, with different molecular weight (465 000) and 435 000, respectively). The two forms of enzyme can be separated by ion-exchange chromatography or polyacrylamide gel electrophoresis. Their subunit structures were compared by sodium dodecylsulfate gel electrophoresis, the only observed difference between the two enzymes is in the molecular weight of the heaviest subunit which is 220 000 for enzyme BI and 180 000 for enzyme BII. Otherwise, the two enzymes have seven common subunits of molecular weights 150 000, 45 000, 26 000, 22 500, 14 500, 12 500 and 9000. Two additional polypeptide chains of 32 000 and 16 500 Mr are dissociated from the enzyme upon polyacrylamide gel electrophoresis or DEAE Sephadex chromatography. The largest subunit of enzyme BI (Mr 220 000) can be specifically cleaved in vitro by a yeast protease extract, generating a polypeptide chain indistinguishable from the largest subunit of enzyme BII. This proteolytic cleavage of enzyme BI in vitro is inhibited by phenylmethylsulfonyl fluoride and does not significantly change the activity of the enzyme with single-stranded or double-stranded DNA as template. The precursor-product relationship of the different forms of class B RNA polymerases in eukaryotic cells is discussed.
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PMID:Two forms of RNA polymerase B in yeast. Proteolytic conversion in vitro of enzyme BI into BII. 78 Jan 8


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