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)

Preparations of recombinant reverse transcriptase RSV were isolated from E. coli HB101/pMF14 cell cultures. The enzyme purified to homogeneity was shown to be made up of two subunits with molecular masses of 97 +/- 4 and 61 +/- 3 kDa. A comparison of enzymatic properties of recombinant transcriptase to those of the enzyme isolated from the RSV (Rauss sarcoma) virus demonstrated that in the preparations under study the recombinant reverse transcriptase exists in a subunit form, alpha beta, and may acquire a relatively stable configuration, alpha 2.
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PMID:[Recombinant RNA-dependent DNA-polymerase from Rous sarcoma virus. Isolation and properties]. 169 35

This study has evaluated changes in RNA synthesis in livers under the distant influence of a malignant tumor. A transplantable-induced sarcoma (MCG 101), transplanted on inbred adult mice (C57BL/6J), was used. Activities of DNA-dependent RNA polymerase (EC 2.7.7.6) were measured in relation to RNA content and translational activity. Liver nuclei from freely fed sarcoma-bearing mice had increased RNA synthesis. As a consequence of this, RNA content per DNA was increased in liver tissue. This was independent of depressed food intake and malnutrition. Elevated RNA synthesis, proportional to the tumor burden was due to an increased proportion of chromatin-engaged RNA polymerase I and II activities. RNA polymerase III activity (template-engaged form) was unchanged when evaluated in isolated nuclei, but appeared to be increased in partially purified extracts of nuclei. RNA content in tumor-host liver was a composite of increased levels of rRNA and tRNA, whereas the levels of poly(A)+ mRNA could not be measured as increased. Overall translational activities in vitro of mRNA from liver tissue of tumor-bearing, pair-weighed, and freely fed tumor-free controls were qualitatively and quantitatively different. mRNA from tumor-bearing mice directed an increased synthesis, particularly of larger proteins (above 55,000 daltons) compared with control animals. The results support the conclusion that previous evidence of elevated net protein synthesis in tumor-host liver is accompanied by increased transcription of genes coding for RNA and also for some or several hepatic proteins.
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PMID:Nuclear RNA polymerase activity in tumor-host livers. 241 3

A random transcription system was used to analyze RNA chain-elongation complexes with RNA polymerases I and II from mouse ascites sarcoma cells. The molecular size of synthesized RNA was analyzed to characterize the elongation reaction by RNA polymerases. The RNA chain-elongation complex after initiation of RNA synthesis on denatured DNA by RNA polymerase II was not decomposed with heparin which dissociated the DNA-RNA polymerase complex, whereas the elongation complex on denatured DNA by RNA polymerase I was more susceptible to decomposition with heparin. RNA transcribed by RNA polymerase I on denatured DNA 30 min after the start of the reaction contained large RNA around 28S and small RNA. The small RNA could be formed by reinitiation and early termination of elongation. RNA transcribed by RNA polymerase II on denatured DNA was only large RNA around 28S. The elongation reaction by RNA polymerases I and II on denatured DNA was not inhibited by rifamycin AF/013, an inhibitor of initiation. These results suggest that RNA polymerase II could synthesize large transcripts without reinitiation and early termination of elongation and that RNA polymerase II formed more a stable elongation complex on denatured DNA than RNA polymerase I.
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PMID:Stability of RNA chain elongation complexes formed with RNA polymerase and denatured DNA templates. 248 21

Elevated protein synthesis in mouse tumor-host liver is the net result of both stimulatory and inhibitory responses. This study compares the directional change in transcription and synthesis of liver and plasma proteins in tumor-host liver as compared with para-neoplastic conditions, such as malnutrition, inflammation, benign cell proliferation and protein deficiency. A methylcholanthrene-induced sarcoma was used in weight stable mice (C57BI/6J). Inflammation was induced by s.c. turpentine injection, and benign cell proliferation by injection of heat-killed Corynebacterium parvum. DNA-dependent RNA-polymerase activity (I, II and III) (EC2.7.7.6) was measured in isolated hepatic nuclei. Protein synthesis was measured by labelling of hepatic and plasma proteins following the injection of a "flooding dose" of the labelled amino acid. Benign hepatic cell proliferation and sterile inflammation caused increased rates of transcription, while malnourished and healthy control animals had lower hepatic transcription than animals bearing a malignant tumor. Inflammation was associated with increased activities of free (nonchromatin engaged) RNA polymerase, which was not found in any other para-neoplastic condition or in the tumor-host liver. A protein- and calorie-deficient state was associated with depressed hepatic and plasma protein synthesis compared with the tumor condition. Tumor-host livers had a nonsecretory protein synthesis rate equal to that of normal livers, but 45% higher plasma protein synthesis. Animals with inflammation and benign cell growth had liver protein synthesis rates which were approximately 50% higher than in tumor-bearing animals, but plasma protein synthesis in tumor-bearing animals was comparable with that of animals which had inflammation. Benign cell growth was not associated with an overall elevated plasma protein synthesis. The translation rate per transcription activity was highest in normal animals and decreased in animals suffering from either tumor, protein deficiency or benign cell proliferation. Hepatic protein synthesis in tumor-host livers is high considering the degree of anorexia and malnutrition, although not as high as in livers from animals with pronounced inflammation. This counter-regulation in tumor-host livers may indicate a compensatory state to maintain protein synthesis against attenuating factors such as the declining food intake. Protein metabolism in tumor-host livers represents an unusual combination of findings.
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PMID:RNA polymerase activity and protein synthesis in mouse tumor-host liver compared to benign para-neoplastic reactions. 341 72

To examine the RNA polymerase (EC 2.7.7.6) specificity of RNA maturation/utilization and transcriptional enhancement, we constructed a chimeric plasmid (pPolI-CAT) in which a promoter for mouse rRNA gene transcription was placed adjacent the coding sequences for chloramphenicol acetyltransferase (CAT; EC 2.3.1.28). A number of other constructs, including plasmids also containing a murine sarcoma virus enhancer or lacking any natural eukaryotic promoter sequences, were also prepared. In apparent agreement with earlier conclusions that an RNA polymerase I transcript can act as a messenger RNA, transient transfection of mouse L cells with pPolI-CAT yielded both high levels of transcription from the RNA polymerase I promoter and enzymatically active CAT protein. However, further examination revealed that CAT protein is not translated from RNA that begins at the normal rRNA transcription initiation site. Polysomal RNA is devoid of such RNA and instead consists of CAT-encoding transcripts that begin elsewhere in the mouse ribosomal DNA (rDNA) region. Since transcription of these aberrant RNAs is stimulated by the addition of a murine sarcoma virus enhancer segment, they are probably transcribed by RNA polymerase II. Transcripts that map to the authentic rRNA start site are not similarly enhanced. Moreover, unlike the RNAs deriving from the rRNA initiation site, these aberrant RNAs are more stable and the level of translatable CAT transcripts is suppressed by inclusion of larger segments of the rDNA promoter regions. Fortuitously initiated mRNAs are also formed in the absence of any natural eukaryotic promoter sequence. From these data we conclude that there is no evidence that normal RNA polymerase I transcription yields functional mRNA and that transcriptional enhancement appears to be RNA polymerase specific.
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PMID:RNA polymerase specificity of mRNA production and enhancer action. 346 18

Ten ribonucleic acid (RNA) tumor viruses grown in five different host cell species and three non-oncogenic viruses from three different virus groups have been examined for ribonuclease H content. Three different substrates were used to assay ribonuclease H: calf thymus [(3)H]RNA-deoxyribonucleic acid (DNA) hybrid prepared with denatured calf thymus DNA and Escherichia coli DNA-directed RNA polymerase, (3)H-polydenylic acid [(3)H-poly(A)] complexed to polydeoxythymidylic acid [poly(dT)], and (3)H-polyuridylic acid [(3)H-poly(U)] complexed to polydeoxyadenylic acid [poly(dA)]. All ten RNA tumor viruses contained ribonuclease H activity which degraded the RNA of both the calf thymus hybrid and poly(A)-poly(dT), whereas only the ribonuclease H in the Moloney strain of murine sarcoma-leukemia virus and in RD-feline leukemia virus hydrolyzed the RNA strand of poly(U)-poly(dA). No appreciable ribonuclease H activity was detected in influenza, Sendai, or vesicular stomatitis virus. The ribonuclease H and RNA-directed DNA polymerase activities in Moloney murine sarcoma-leukemia virus were inseparable by phosphocellulose chromatography or glycerol gradient centrifugation, but appeared to be partially separated by diethylaminoethyl-cellulose chromatography.
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PMID:Ribonuclease H: a ubiquitous activity in virions of ribonucleic acid tumor viruses. 411 67

The availability of a purified RNA-instructed DNA polymerase (reverse transcriptase) from avain myeloblastosis virus provided the opportunity to explore whether this enzyme could be used as a general tool for synthesizing DNA complements of a wide variety of natural RNAs. The results described show that this potentially useful situation is in fact realized. The avian viral transcriptase can mediate the synthesis of DNA complementary to RNAs of such widely divergent origins as Qbeta bacteriophage and Moloney sarcoma virus. These findings open up novel pathways for the experimental resolution of several interesting problems. Thus, given a purified RNA message, one should be able to synthesize the corresponding DNA genetic material. If suitably labeled, the synthetic DNA has various obvious uses, including its use via molecular hybridization as an analytical probe for the corresponding gene on the chromosomes or for its message in a complex mixture of RNA molecules. Of immediate practical interest is the import of these findings for viral oncology. They imply that for many purposes we will not be compelled to isolate or use the "reverse transcriptase" from each oncogenic virus in order to synthesize its complementary DNA. The ability of one enzyme to accept a variety of oncogenic RNAs will obviate many of the logistical difficulties that arise, particularly in attempts to illuminate the etiology of human cancer.
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PMID:Synthesis of DNA complements of natural RNAs: a general approach. 433 Sep 45

Fourteen streptovaricin derivatives were tested for inhibition of cellular nucleotide polymerases (deoxyribonucleic acid polymerases alpha, beta, and gamma, terminal deoxynucleotidyltransferase [TdT], and ribonucleic acid polymerase II), simian sarcoma virus deoxyribonucleic acid polymerase, and herpes simplex virus type 1-induced deoxyribonucleic acid polymerase (HSV-DP). Three compounds (strep-tovadienal C, prestreptovarone, and streptoval Fc) preferentially inhibited TdT and HSV-DP over the other enzymes. These compounds inhibited HSV-DP more potently than they inhibited TdT. Evidence indicated that the mode of inhibition of TdT and HSV-DP by streptovadienal C and prestreptovarone was by interaction with the enzymes and not with template-primer, initiator, substrates, or divalent cations required for enzyme activity. Furthermore, data suggested that these compounds bind with greater affinity to HSV-DP than to TdT. Streptovadienal C and prestreptovarone were examined for their effect on the replication of herpes simplex virus type 1 in African green monkey kidney (CV1) cells. These compounds produced 2- and 3-log drops in virus titer, respectively, at concentrations not significantly affecting cell viability. This correlated with evidence indicating a greater binding affinity of these compounds for HSV-DP over cellular nucleotide polymerases.
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PMID:Inhibition of cellular and virus-associated nucleotide polymerases by, and anti-herpes simplex virus activity of, streptovaricin derivatives. 611 56

On the basis of our observation of the increased specific activities of glutamine-utilizing enzymes in purine and pyrimidine metabolism in hepatoma 3924A, and because the concentration of glutamine is ten times lower in the hepatomas than in the liver, the biochemical pharmacology of the anti-glutamine agent, acivicin, was examined. (1) Acivicin competitively inhibited the activities of amidophosphoribosyl-transferase, CTP synthetase and carbamoyl-phosphate synthetase II from extracts of liver and hepatoma 3924A. (2) In addition to the competitive inhibition exerted by acivicin, evidence was obtained that this drug also irreversibly inactivated in vitro the glutamine-utilizing enzymes. It is particularly relevant for the selectivity of acivicin that the activity of aspartate carbamoyltransferase, an enzyme present in the same complex as carbamoyl-phosphate synthetase II, was not affected by the anti-glutamine agent. (3) Acivicin in vivo brought down the activities of glutamine-utilizing enzymes in a period of 10 min to 1 hr after injection. CTP synthetase activity declined to less than 10% of that observed in the uninjected rats. The decreases were not reversible by various in vitro methods, but in vivo the activities returned to normal range in 72 hr. (4) The activity of aspartate carbamoyltransferase, which exists as a multi-enzyme complex with synthetase II, was not altered by acivicin injection. Similar results were observed in transplantable sarcoma in the rat. (5) The acivicin-induced decrease in enzymic activities could not be restored by purification of the enzymes. (6) In vitro studies indicated that addition of acivicin to liver or hepatoma extracts or purified enzymes rapidly decreased enzymic activities; the activities could not be restored. These results are consistent with an interpretation that acivicin acts either as a tight-binding inhibitor or as an inactivator through alkylation of the enzymes of glutamine utilization. (7) Acivicin in combination with actinomycin provided a synergistic kill of hepatoma cells in tissue culture and also inhibited the growth of transplantable solid hepatoma 3924A in the rat. (8) The synergistic biological results of combination chemotherapy with acivicin and actinomycin can be accounted for by the action of acivicin in inhibiting GMP and CTP synthetases, resulting in a decrease in GTP and CTP content, and by the actinomycin-caused inhibition of RNA polymerase in selectively blocking the utilization of GTP and CTP.
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PMID:Multi-enzyme-targeted chemotherapy by acivicin and actinomycin. 618 Jun 9

We have investigated the ability of molecularly cloned murine type C retroviral DNA to direct accurate initiation of RNA synthesis when added to cell-free extracts. Two different cloned proviruses were used. The first was derived from an integrated molecule of AKR murine leukemia virus and contains adjacent host information. The origin of the second was an unintegrated permuted copy of Harvey murine sarcoma virus. We found that the leukemia virus cloned provirus, as predicted by structural considerations, contained two functional RNA polymerase II promoters located in the U3 region present at either end of the molecule. These promoters initiate transcription at equal rates in vitro. We also found that the permuted sarcoma virus clone contained an RNA polymerase II promoter in the U3 region. Removal of viral sequences 49 bases upstream of the in vitro sarcoma virus initiation site by restriction cleavage results in loss of specific transcription, indicating a role for this information in in vitro promotion. The 5' ends of in vitro and in vivo viral RNA were compared by nuclease mapping techniques and found to be identical. Based on this evidence, we conclude that murine retroviral genomes contain sufficient information to initiate transcription independent of any host information in vitro and that these viral promoters are probably also active in vivo. In addition to the promoter in U3, Harvey murine sarcoma virus contains a second promoter in vitro that initiates near the 5' boundary of the transformation-specific (src) region of the virus. Initiation by this promoter was insensitive to low levels of alpha-amanitin, and the RNA transcript could be terminated to yield a 340-nucleotide product.
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PMID:Specific transcriptional initiation in vitro on murine type C retrovirus promoters. 627 Jun 79


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