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)

When bacterial lipopolysaccharide, a B-cell mitogen, was injected intraperitoneally into mice, the rate of deoxyribonucleic acid synthesis and the number of antibody-secreting cells in the spleen increased simultaneously, reaching a maximum in 3 days. The rate of ribonucleic acid synthesis also increased during this period, and this was found to be due to activation of alpha-amanitin-sensitive transcription in lymphoid cells of the spleen. The factors stimulating ribonucleic acid polymerase II in the spleens of normal mice and those treated with lipopolysaccharide were compared, and an additional factor besides that present in normal spleens was found in the spleen of lipopolysaccharide-treated mice.
 ...
PMID:Bacterial lipopolysaccharide induction of a mouse spleen factor stimulating ribonucleic acid polymerase II. 32 12

Experimental infections with Coxiella burnetii augment rates of ribonucleic acid (RNA) synthesis in guinea pigs. The activity of deoxyribonucleic acid-dependent RNA polymerase in L cells persistently infected with C. burnetii was threefold greater than that in unifected cells; the polymerase activity in infected cells was predominantly of class I, whereas that in uninfected cells was predominantly of class II. A search for regulatory factors of polymerase activity revealed that preincubation of uninfected L cells with lipopolysaccharide of C. burnetii or with putrescine, spermidine, or spermine enhanced polymerase activities. Because sonicated nuclei were assayed rather than purified enzymes, it cannot be stated definitely whether augmented polymerase activites were consequences of direct effects of infection on polymerases or a triggering of secondary regulatory factors.
 ...
PMID:Effects of infection with Coxiella burnetii on synthesis of RNA in L cells. 64 91

We have cloned a gene from a Salmonella typhimurium with the ability to complement the rfaC mutation (heptose-deficient lipopolysaccharide, sensitivity to rough-specific bacteriophages, and susceptibility to hydrophobic antibiotics). A 1018-base pair EcoRV-Tth111I fragment, subcloned into the pBluescriptKS+ vector to yield pKZ103, retains complementing activity. Nucleotide sequencing revealed an open reading frame corresponding to a protein of 317 amino acids (M(r) approximately 35,100). The plasmid pKZ103, which has a properly aligned T7 promoter, can overexpress a protein of M(r) = 31,000 when T7 RNA polymerase is supplied. An in vitro system was established for analysis of heptose addition to the precursor [4'-32P](KDO)2-IVA (Brozek, K. A., Hosaka, K., Robertson, A. D., and Raetz, C. R. H. (1989) J. Biol. Chem, 264, 6956-6966). Soluble fractions from wild-type or heptose-deficient rfa mutants were tested for their ability to convert [4'-32P](KDO)2-IVA to more polar substances. In wild-type extracts, these conversions required addition of ATP or ADP-heptose. In extracts of rfaC-, rfaD-, or rfaE-deficient strains, no polar products were observed with ATP. ADP-heptose restored synthesis in rfaD and rfaE but not rfaC extracts, indicating that rfaD and rfaE are involved in ADP-heptose formation. When the cloned rfaC gene was introduced into an rfaC-deficient mutant, extracts from such cells regained the ability to metabolize [4'-32P](KDO)2-IVA, showing that rfaC encodes the enzyme that attaches the proximal heptose to lipopolysaccharide.
 ...
PMID:The rfaC gene of Salmonella typhimurium. Cloning, sequencing, and enzymatic function in heptose transfer to lipopolysaccharide. 152 14

Anti-Fc gamma R IgM monoclonal antibodies (mAbs) isolated from lipopolysaccharide-stimulated spleen cells from tightskin (TSK) mice were found to be polyspecific, reacting with a wide variety of molecules, including double-stranded DNA, topoisomerase, RNA polymerase, and different collagen types. Approximately 60% of the polyspecific IgM mAbs have anti-Fc gamma R specificity. These anti-Fc gamma R mAbs induce the release of hydrolases from both azurophil and specific granules of human neutrophils. 25-45% of the total cellular content (determined in Nonidet P-40 lysates) of neutrophil elastase, 10-25% of beta-glucuronidase, and 30-50% of alkaline phosphatase was released after incubation with the mAbs. The degranulation process was accompanied by dramatic morphological changes shown by scanning and transmission electron microscopy. The release of hydrolytic enzymes stimulated by the IgM anti-Fc gamma R mAbs was inhibited by preincubation of neutrophils with Fab fragments of either anti-human Fc gamma RII (IV.3) or anti-human Fc gamma RIII (3G8) mAbs. The binding of the anti-Fc gamma R TSK mAbs to human neutrophils was inhibited by Fab fragments of mAb 3G8. However, we found that the TSK anti-Fc gamma R mAbs do not bind to human Fc gamma RII expressed in either CHO cells or the P388D1 mouse macrophage cell line. Since the enzyme release could be inhibited by Fab fragments of mAb IV.3, we suggest that the signal transduction may require Fc gamma RII activation subsequent to crosslinking of the glycan phosphatidyl inositol-anchored Fc gamma RIII-1. These data demonstrate for the first time that polyspecific autoantibodies with Fc gamma R specificity can trigger neutrophil enzyme release via human Fc gamma RIII-1 in vitro and indicate a possible role for such autoantibodies in autoimmune inflammatory processes.
 ...
PMID:IgM anti-Fc gamma R autoantibodies trigger neutrophil degranulation. 182 27

The synthesis of ribosomal RNA (rRNA) in murine B lymphocytes is markedly elevated in response to mitogens such as lipopolysaccharide (LPS). First, to investigate the mechanism involved, antibodies directed against RNA polymerase I, the enzyme responsible for transcription of ribosomal genes, were introduced into the cytoplasm of lymphocytes via red cell-mediated microinjection and the ability of cells to synthesize RNA was examined. Simultaneous immunofluorescence/autoradiography revealed that 7% or less of the cells injected with specific antibodies prior to stimulation were actively synthesizing rRNA 15 or 40 h following LPS addition. In contrast 19% and 27% of cells injected with control IgG were active at these times. Non-ribosomal RNA synthesis was unaffected by the presence of anti-RNA polymerase I antibodies. Since antibodies injected into the cytoplasm were limited to that compartment, these data suggest that rRNA synthesis induced by LPS requires translocation of cytoplasmic RNA polymerase I into the nucleus. Second, to test whether synthesis of rRNA is required for entry into S phase, the effect of anti-RNA polymerase I antibodies on DNA synthesis in response to LPS was evaluated. Only 7% of cells containing anti-RNA polymerase I antibodies had initiated DNA synthesis 40 h after LPS addition whereas 25% of cells containing control IgG were actively synthesizing DNA at that time. These results suggest that nuclear accumulation of RNA polymerase I and increased rRNA synthesis are required for LPS-induced DNA synthesis in B lymphocytes.
 ...
PMID:Cytoplasmic to nuclear translocation of RNA polymerase I is required for lipopolysaccharide-induced nucleolar RNA synthesis and subsequent DNA synthesis in murine B lymphocytes. 278 28

When murine resting B cells are polyclonally stimulated by bacterial lipopolysaccharide (LPS) in vitro for a short period of 4 days, they are activated to DNA synthesis and cell division, and they also differentiate to immunoglobulin (Ig)-secreting plasma cells. These two events are accompanied with several qualitative changes at the Ig mRNA level: the disappearance of delta mRNA after stimulation, the switch from membrane to secretory form of mu-mRNA, and the late appearance of IgM joining chain (J-chain) mRNA. There is also a quantitative increase of Ig-gene expression at the level of: Ig gene transcription, mu-, kappa- and J-chain mRNA accumulation, and Ig translation and secretion. A comparison of Ig transcription rates before and in the course of LPS stimulation, as determined by in vitro transcriptional run-on assays, has shown that there is a large increase of the RNA polymerase density on both mu- and kappa-loci (30-60-fold), which is quantitatively comparable with the accumulation of both mu- and kappa-mRNAs at the steady state mRNA level. These data therefore suggest that former results obtained with tumor cells regarding post-transcriptional control of Ig gene expression do not reflect the physiological behavior of normal B cells with respect to the molecular events of B cell triggering. We also propose that additional molecular events such as RNA processing and the transcriptional activation of J-chain gene might be essential for controlling the maximal transcriptional rate across the Ig loci.
 ...
PMID:Transcriptional control of mu- and kappa-gene expression in resting and bacterial lipopolysaccharide-activated normal B cells. 311 52

The acute monocytic leukemia cell line THP-1 secretes predominantly IL-1 beta after treatment with bacterial lipopolysaccharide and tumour promoting phorbol ester (PMA). IL-1 alpha is also secreted, but represents less than 10% of the total IL-1 activity. This differential is reflected at the level of mRNA as IL-1 beta mRNA is more abundant than IL-1 alpha mRNA. Studies of transcription in isolated nuclei however indicate that each gene is transcribed at a similar rate, suggesting that post-transcriptional mechanisms regulate the relative abundance of IL-1 alpha and IL-1 beta mRNA. Measurement of RNA half life after addition of alpha-amanitin (an inhibitor of RNA polymerase II) indicate that IL-1 alpha mRNA is not as stable as IL-1 beta mRNA suggesting one mechanism for the different relative levels of RNA.
 ...
PMID:Post-transcriptional control of IL-1 gene expression in the acute monocytic leukemia line THP-1. 326 53

The effect of lipopolysaccharide on RNA polymerase I activity in primary cultures of murine B lymphocytes has been examined. In cells treated with mitogen for 48 h, the activity of RNA polymerase I was approximately 15 times greater than in control cells. In situ localization of RNA polymerase I using indirect immunofluorescence indicated that there was at least a 10-fold increase in the amount of this enzyme associated with nucleoli of 48 h mitogen-treated cells relative to control cells. Immunoblotting experiments demonstrated a similar increase in the concentration of the 190-kDa subunit bound to DNA; the concentrations of the other polymerase I-associated polypeptides did not correlate with rRNA synthesis. Assuming 1 mol of the 190-kDa polypeptide/mol of polymerase I, it was estimated that 2,300 and 30,000 molecules of enzyme were associated with rDNA in the unstimulated and stimulated B cell, respectively. Thus, an increased cellular concentration of the 190-kDa subunit of RNA polymerase I and its association with ribosomal DNA may be a crucial step in rRNA synthesis.
 ...
PMID:Lipopolysaccharide-mediated induction of RNA polymerase I activity and amount in murine B lymphocytes. 352 71

The foregoing studies are intended to define a differentiation process and to permit genetic access to the mechanisms that control this process. In order to elucidate the basic mechanisms whereby a cell dictates its own defined morphogenic changes, we have found it helpful to study an organism that can be manipulated both biochemically and genetically. We have attempted to develop the studies initiated by Poindexter,Stove and Stanier, and Schmidt and Stanier (16, 17, 20) with the Caulobacter genus so that these bacteria can serve as a model system for prokaryotic differentiation. The Caulobacter life cycle, defined in synchronously growing cultures, includes a sequential series of morphological changes that occur at specific times in the cycle and at specific locations in the cell. Six distinct cellular characteristics, which are peculiar to these bacteria, have been defined and include (i) the synthesis of a polar organelle which may be membranous (21-23), (ii) a satellite DNA in the stalked cell (26), (iii) pili to which RNA bacteriophage specifically adsorb (16, 33), (iv) a single polar flagellum(17), (v) a lipopolysaccharide phage receptor site (27), and (vi) new cell wall material at the flagellated pole of the cell giving rise to a stalk (19, 20). Cell division, essential for the viability of the organism, is dependent on the irreversible differentiation of a flagellated swarmer cell to a mature stalked cell. The specific features of the Caulobacter system which make it a system of choice for studies of the control of sequential events resulting in cellular differentiation can be summarized as follows. 1) Cell populations can be synchronized, and homogeneous populations at each stage in the differentiation cycle can thus be obtained. 2) A specific technique has been developed whereby the progress of the differentiation cycle can be accurately measured by adsorption of labeled RNA phage or penetration of labeled phage DNA into specific cell forms. This technique can be used to select for mutants blocked in the various stages of morphogenesis. 3) Temperature-sensitive mutants of Caulobacter that are restricted in macromolecular synthesis and development at elevated temperatures have been isolated. 4) Genetic exchange in the Calflobacter genus has been demonstrated and is now being defined. Two questions related to control processes can now readily be approached experimentally. (i) Is the temporal progression of events occurring during bacterial differentiation controlled by regulator gene products? (ii) Is the differentiation cycle like a biosynthetic pathway where one event must follow another? The availability of temperature-sensitive mutants blocked at various stages of development permits access to both questions. An interesting feature of the differentiation cycle is that the polar organelle may represent a special segregated unit which is operative in the control of the differentiation process. Perhaps the sequential morphogenic changes exhibited by Caulobacter are dependent on the initial synthesis of this organelle. Because the ultimate expression of cell changes are dependent on selective protein synthesis, specific messenger RNA production-either from DNA present in an organelle or from the chromosome-may prove to be a controlling factor in cell differentiation. We have begun studies with RNA polymerase purified from Caulobacter crescentus to determine whether cell factors or alterations in the enzyme structure serve to change the specificity of transcription during the cell cycle. Control of sequential cell changes at the level of transcription has long been postulated and has recently been substantiated in the case of Bacillus sporulation (6). The Caulobacter bacteria now present another system in which direct analysis of these control mechanisms is feasible.
 ...
PMID:Bacterial differentiation. 557 65

RNA synthesis during macrophage activation with lipopolysaccharide (LPS) was analyzed in mice. The RNA synthesis of macrophages was considerably increased early after LPS stimulation, but drastically decreased at a later period. The decrease of RNA synthesis was observed in mouse strains responding to LPS such as BALB/c, ATL and ddY, but not in nonresponder strain, C3H/HeJ. Furthermore, the decrease of RNA synthesis occurred in both alpha-amanitin resistant and sensitive RNA polymerase reactions. However, RNA polymerases in nuclei were not changed significantly in LPS-treated macrophages, but the factors affecting RNA polymerase reactions were drastically changed. Amongst these factors, the stimulating factors were decreased and a novel repressing factor was remarkably increased. The factors were partially characterized and their significance in macrophage activation is discussed.
 ...
PMID:A decrease of RNA synthesis during macrophage activation with lipopolysaccharide--an association with novel regulating factors. 608 77


1 2 3 4 5 6 7 8 9 10 Next >>