Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.6 (RNA polymerase)
34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

UV irradiation of infectious vesicular stomatitis virus was employed to study the relationship between the expression of certain viral gene functions and viral inhibition of RNA synthesis in mouse myeloma (MPC-11) cells. Viral infectivity, protein synthesis, and viral mRNA synthesis were all highly susceptible to inactivation by UV radiation; however, low levels of viral transcriptase activity were detected in vitro in virus preparations subjected to large doses of UV radiation. In sharp contrast, the capacity of vesicular stomatitis virus to shut off cellular transcription was quite resistant to UV radiation. The data presented here indicate that viral transcription is essential to inhibit host RNA metabolism, even though synthesis of viral polypeptides in the inhibited cells could not be detected. At those levels of UV radiation that inactivated all viral gene functions, except viral inhibition of cellular RNA synthesis, the only viral product detected was non-adenylated, low-molecular-weight RNA species.
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PMID:Use of UV irradiation to identify the genetic information of vesicular stomatitis virus responsible for shutting off cellular RNA synthesis. 9 Jan 65

Infection of mouse myeloma (MPC-11) cells with vesicular stomatitis virus resulted in rapid loss in activity of cellular RNA polymerases associated with nuclear chromatin. No RNA polymerase inhibitor could be detected in extracts of infected cell nuclei. Reconstitution experiments with solubilized RNA polymerases dissociated from chromatin of infected and uninfected cells demonstrated that vesicular stomatitis viral infection did not affect the ability of the polymerases to function on endogenous or exogenous templates; nor did infection alter the template capability of the chromatin. Measurement of the number of actively growing RNA chains revealed that infected cell nuclei contained fewer active polymerase units; however, the rates of RNA chain elongation were the same in nuclei from infected and uninfected cells. Quantitation of the number of polymerase units active in nuclear chromatin revealed that the alpha-amantin-sensitive polymerase II was more severely reduced by viral infection than were polymerases I and III.
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PMID:Vesicular stomatitis virus infection reduces the number of active DNA-dependent RNA polymerases in myeloma cells. 22 70

Partially thiolated polycytidylic acid (MPC), a representative member of the "antitemplate" class of novel chemotherapeutic agents, is a potent inhibitor of the E. coli DNA-dependent RNA polymerase. It inhibited 50% of the enzymic reaction at a concentration of 6 micrometers. Kinetic studies indicated that MPC had no effect on the chain elongation of the transcription process, but it appeared to inhibit the initiation of RNA synthtesis presumably by competing with the DNA template for binding to the RNA polymerase. Binding studies, using a gel filtration method, showed that MPC and the RNA polymerase formed a stable complex which was not dissociated by 0.3 M NaCl. It is inferred that mixed disulfide linkage(s) might have been formed between the enzyme and MPC. The implications of these findings are discussed.
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PMID:Studies on the mode of action of partially thiolated polycytidylic acid (MPC), a novel type of antineoplastic agent. 38 53

To investigate the chromatin surrounding an active gene, we have determined the distribution of RNA polymerase molecules, the intactness of nucleosomal structure, and the subnuclear compartmentalization along 15 kilobase pairs (kb) of the mouse kappa immunoglobulin locus of MPC-11 plasmacytoma cells. Hybridization of in vitro nuclear transcripts to probes specific for the template strand reveals that transcription terminates within the region between 1.1 and 2.3 kb downstream from the poly(A) addition site. Ten different short sequences (8-13 base pairs) reside within 460 base pairs of this termination region that exhibit homology with sequences found in the termination regions of mouse beta-globin and chicken ovalbumin genes. Transcription of the nontemplate strand occurs on either side of this termination region. We find that both within the transcription unit and 6.5 kb downstream of the termination region of the kappa gene, the canonical nucleosomal structure is perturbed, the chromatin exhibits pronounced insolubility, and the nucleosomes liberated by micrococcal nuclease appear to lack histone H1. The insolubility is characterized by interactions that are disrupted by 0.3 to 0.6 M NaCl treatment. We conclude that the active chromatin phenotype spreads a considerable distance along the kappa locus, well beyond the region of transcription termination.
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PMID:Transcription termination and chromatin structure of the active immunoglobulin kappa gene locus. 308 10

Plasmacytomagenesis provides a murine model to decipher progressive genetic events culminating in a B-cell neoplasia. Activation of the c-myc protooncogene by chromosomal translocation is considered an initiating event. Intracisternal A-type particles (IAPs) are defective retroviral-like structures present in the endoplasmic reticulum of plasmacytomas (PCTs). IAP proviral insertions have been documented to engender negative or positive effects on the expression of nearby cellular genes. We have isolated a gene, PANG (plasmacytoma-associated neuronal glycoprotein), that is ectopically transcribed in a number of PCTs due to IAP long terminal repeat (LTR) activation. A full-length PANG cDNA was isolated from an MPC-11 plasma cell tumor cDNA library and encodes a polypeptide of about 113 kDa with six immunoglobulin C2-like and four type III fibronectin-like domains. PANG bears a striking resemblance to axonal glycoproteins TAG-1 and F11 known to function in neuronal outgrowth. An extensive survey revealed a predominant 3.6-kb PANG transcript in 60% (30 of 50) of PCTs as well as unique smaller and larger species. All other normal and transformed lymphoid and nonlymphoid cell lines and normal tissues were negative for PANG expression except for the brain, wherein unique 4.0- and 6.1-kb transcripts were detected. Reverse transcriptase PCR analysis revealed IAP LTR fusion to PANG mRNAs in five PCTs and in a neuroblastoma line. The 5' end of a mouse brain PANG cDNA was identical to the MPC-11 PANG transcript except for the precise replacement of its 5' LTR sequence.
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PMID:PANG, a gene encoding a neuronal glycoprotein, is ectopically activated by intracisternal A-type particle long terminal repeats in murine plasmacytomas. 810 13