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)

The BglG protein is a transcriptional antiterminator acting within the beta-glucoside operon of Escherichia coli by binding to a specific sequence motif in the growing mRNA. Binding of BglG prevents formation of the terminator stem-loop structure, thereby causing the RNA polymerase to continue transcription. Activity of BglG is modulated in a complex way by antagonistically acting phosphorylations in response to the availability of beta-glucosidic substrates and to the catabolic state of the cell. The enzymes responsible for these phosphorylations are members of the phosphoenolpyruvate:carbohydrate phosphotransferase system (PTS) that represents a central carbohydrate uptake and signal transduction system. As these enzymes are believed to all form higher-order complexes associated with the cytoplasmic membrane, we tested whether or not BglG would remain active when artificially anchored to its presumptive site of regulation, the inner membrane. We show that the membrane-anchored protein indeed efficiently catalyzes transcriptional antitermination. Moreover, the membrane-attached BglG remains regulated by the PTS. Thus, a membrane-bound regulatory RNA binding protein can potentially interact fast enough with its target within the nascent transcript and cause the transcriptional machinery to proceed, before transcriptional termination would occur. Consequently, there is no principal necessity for an RNA-binding transcriptional regulator like BglG to leave the inner membrane, a potential regulatory site, and migrate to the site of transcription, the nucleoid.
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PMID:Efficient transcriptional antitermination from the Escherichia coli cytoplasmic membrane. 1132 58

The budding yeast transcriptional activator Gcn4 is rapidly degraded in an SCF(Cdc4)-dependent manner in vivo. Upon fractionation of yeast extracts to identify factors that mediate Gcn4 ubiquitination, we found that Srb10 phosphorylates Gcn4 and thereby marks it for recognition by SCF(Cdc4) ubiquitin ligase. Srb10 is a physiological regulator of Gcn4 stability because both phosphorylation and turnover of Gcn4 are diminished in srb10 mutants. Gcn4 is almost completely stabilized in srb10Delta pho85Delta cells, or upon mutation of all Srb10 phosphorylation sites within Gcn4, suggesting that the Pho85 and Srb10 cyclin-dependent kinases (CDKs) conspire to limit the accumulation of Gcn4. The multistress response transcriptional regulator Msn2 is also a substrate for Srb10 and is hyperphosphorylated in an Srb10-dependent manner upon heat-stress-induced translocation into the nucleus. Whereas Msn2 is cytoplasmic in resting wild-type cells, its nuclear exclusion is partially compromised in srb10 mutant cells. Srb10 has been shown to repress a subset of genes in vivo, and has been proposed to inhibit transcription via phosphorylation of the C-terminal domain of RNA polymerase II. We propose that Srb10 also inhibits gene expression by promoting the rapid degradation or nuclear export of specific transcription factors. Simultaneous down-regulation of both transcriptional regulatory proteins and RNA polymerase may enhance the potency and specificity of transcriptional inhibition by Srb10.
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PMID:Negative regulation of Gcn4 and Msn2 transcription factors by Srb10 cyclin-dependent kinase. 1133 99

I-mfa (inhibitor of the MyoD family) is a transcription modulator that binds to and suppresses the transcriptional activity of MyoD family members. I-mfa transcripts are expressed in sclerotome, suggesting a role of I-mfa in skeletogenesis. The aim of this study was to examine the expression and regulation of I-mfa in osteoblasts. We found that I-mfa is expressed at a low level in an osteoblast-like cell line, MC3T3E1, and a pluripotent differentiation modulator, 1,25-dihydroxyvitamin D(3), specifically enhanced I-mfa mRNA expression. This effect was completely blocked by the presence of an RNA polymerase inhibitor, but not by a protein synthesis inhibitor, suggesting that 1,25-dihydroxyvitamin D(3) upregulates transcription of the I-mfa gene without requirement for new protein synthesis. Western blot analysis indicated that 1,25-dihydroxyvitamin D(3) increased the I-mfa protein levels severalfold in MC3T3E1 cells. I-mfa expression was also observed in primary mouse calvaria cells and ROS17/2.8 cells and 1,25-dihydroxyvitamin D(3) enhanced I-mfa expression in these cells. These data indicate that I-mfa is a novel transcriptional regulator gene expressed in osteoblasts and that its level is under the control of 1,25-dihydroxyvitamin D(3).
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PMID:Vitamin D(3) enhances the expression of I-mfa, an inhibitor of the MyoD family, in osteoblasts. 1138 74

Thyroglobulin (Tg), has recently been identified as a transcriptional regulator of thyroid-restricted genes. The extrathyroidal expression of several of these genes (including the transcription factor Pax-8) together with the occurrence of specific Tg binding sites suggests a secondary role for Tg as a circulating hormone. In this study, we demonstrate using Northern analysis that Pax-8 is expressed in the mouse mesangial cell, and that its transcript levels are suppressed by Tg. These cells also express an asialoglycoprotein receptor, a receptor involved in Tg endocytosis in the thyroid, and a Tg transcript smaller than the 8.3-kb thyroidal form. Reverse transcriptase PCR showed that suppression of Pax-8 by Tg is correlated with reduced expression of bcl-2 apoptosis suppressor. Tg, but not triiodothyronine (T(3)) significantly increased MC proliferation above control as determined by DNA content of MC cultures. The effect of Tg on proliferation was not duplicated by either bovine serum albumin, gamma-globulins, lactoferrin, or the ASGPR-specific ligand,orosomucoid. These results suggest a possible endocrine role for Tg in regulating both Pax-8 related gene transcription and cell division in the mesangial cell.
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PMID:Thyroglobulin increases cell proliferation and suppresses Pax-8 in mesangial cells. 1145 62

The 321-residue XylS and XylS1 proteins, encoded by the pWW0 and pWW53 plasmids respectively, differ in only 5 residues at positions 4, 53, 90, 137, and 153. As a result, the effector profile of XylS is wider than that of XylS1, and XylS mediates higher levels of transcription from its cognate-regulatable promoter than does XylS1. We generated a series of XylS-pWW0 mutants and found that the single mutants Asp-137-->Glu and His-153-->Asn exhibited an activation pattern different from that of the wild-type regulator. In the double-mutant XylSD137E,H153N the effector profile for benzoates was similar to that of XylS1. This suggests that these two residues are crucial for effector recognition and regulator activation to stimulate transcription. XylS-dependent transcription from its cognate promoter is mediated by RNA polymerase with sigma(32) or sigma(38), whereas XylS1 uses RNA polymerase with sigma(32) or sigma(70). We also found that point mutations at positions 137 and 153 of XylS led RNA polymerase to mediate transcription with sigma(70) rather than with sigma(38), as demonstrated by primer extension analysis in a sigma(70)-thermosensitive background proficient and deficient in sigma(38). This suggests that a positive transcriptional regulator can choose the RNA polymerase complex that mediates transcription from a given promoter.
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PMID:Residues 137 and 153 at the N terminus of the XylS protein influence the effector profile of this transcriptional regulator and the sigma factor used by RNA polymerase to stimulate transcription from its cognate promoter. 1175 34

Affected neurons of Alzheimer disease (AD) brain are distinguished by the presence of the cell cycle cdc2 kinase and mitotic phosphoepitopes. A significant body of previous data has documented a decrease in neuronal RNA levels and nucleolar volume in AD brain. Here we present evidence that integrates these seemingly distinct findings and offers an explanation for the degenerative outcome of the disease. During mitosis cdc2 phosphorylates and inhibits the major transcriptional regulator RNA polymerase II (RNAP II). We therefore investigated cdc2 phosphorylation of RNAP II in AD brain. Using the H5 and H14 monoclonal antibodies specific for the cdc2-phosphorylated sites in RNAP II, we found that the polymerase is highly phosphorylated in AD. Moreover, RNAP II in AD translocates from its normally nuclear compartment to the cytoplasm of affected neurons, where it colocalizes with cdc2. These M phase-like changes in RNAP II correlate with decreased levels of poly-A RNA in affected neurons. Significantly, they precede tau phosphorylation and neurofibrillary tangle formation. Our data support the hypothesis that inappropriate activation of the cell cycle cdc2 kinase in differentiated neurons contributes to neuronal dysfunction and degeneration in part by inhibiting RNAP II and cellular processes dependent on transcription.
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PMID:Hyperphosphorylation of RNA polymerase II and reduced neuronal RNA levels precede neurofibrillary tangles in Alzheimer disease. 1176 94

A novel transcriptional regulator has been identified in the 400-bp upstream region of the guaA gene of Mycobacterium tuberculosis H37Rv that promotes the expression of lacZ gene in Mycobacterium smegmatis mc(2)155 and M. tuberculosis H37Rv but not in Escherichia coli DH5alpha. PCR-mediated deletion mutagenesis and cloning identified a 120-bp fragment upstream from the guaA gene to be the actual regulator. Primer extension analysis mapped the transcription start site to be the first 'G' residue of the translation start codon GTG of the guaA gene. Electrophoretic mobility shift assay showed strong binding of M. smegmatis RNA polymerase holoenzyme to the 400-bp fragment that expresses lacZ in mycobacterial species and a weak binding to the 280-bp fragment that expresses only in E. coli DH5alpha. Both promoter recombinants revealed varied response in the presence of purine nucleotides and exhibited down-regulation when subjected to amino acid starvation.
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PMID:Identification of a novel mycobacterial transcriptional regulator and its involvement in growth rate dependence and stringent control. 1200 15

NahR, a LysR-type transcriptional regulator, is required for expression of naphthalene catabolic operons. However, detailed mechanisms of transcriptional activation by NahR are poorly understood. Many transcriptional activators make direct contact with RNA polymerase (RNAP) to initiate transcription. We investigated the hypothesis that direct contact between NahR and the alpha subunit of RNAP (alphaRNAP) may be involved in expression of the naphthalene catabolic operons in Pseudomonas putida NCIB 9816-4. Interactions between the NahR and alphaRNAP in P. putida NCIB 9816-4 were analyzed using the yeast two-hybrid system. The results obtained indicate that protein-protein interactions occur between alphaRNAP and the NahR. Gene activation by NahR is consistent with the general transcriptional mechanism of class I transcription factors, which function by contacting alphaRNAP.
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PMID:Interaction of NahR, a LysR-type transcriptional regulator, with the alpha subunit of RNA polymerase in the naphthalene degrading bacterium, Pseudomonas putida NCIB 9816-4. 1216 32

CrgA is a LysR-type transcriptional regulator involved in the intimate adhesion of Neisseria meningitidis to target human epithelial cells. It is negatively autoregulated, and its expression is transiently induced upon contact with target cells. We analysed the functional organization of CrgA using in frame deleted proteins. Four truncated proteins were constructed and purified. They were deleted between residues 20 and 40, 121 and 154, 111 and 181 and 268 and 291. Meningococcal mutants harbouring the corresponding deleted crgA alleles were also constructed. All mutants showed a reduced ability to adhere to epithelial cells. beta-Galactosidase activity assays using a crgA-lacZ transcriptional fusion showed that all the mutations except the 268-291 deletion resulted in loss of induction upon contact with target cells. Gel mobility shift assays and cross-linking assays showed that the oligomerization of CrgA is required for DNA binding and that the N-terminal part of CrgA is directly involved in DNA binding through a helix-turn-helix motif. The C-terminal region is also involved in DNA binding, probably by permitting the oligomerization of CrgA. The C-terminal region also seemed to interact with RNA polymerase. Therefore, the binding of CrgA and its interaction with RNA polymerase may inhibit the clearance of meningococcal promoters that are repressed by CrgA during the intimate adhesion of N. meningitidis to target cells.
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PMID:The Neisseria meningitidis adhesion regulatory protein CrgA acts through oligomerization and interaction with RNA polymerase. 1249 59

The sigH gene encodes a sigma factor whose transcription is controlled by stress regulatory systems and the developmental program in Streptomyces coelicolor. Here, we describe developmentally regulated post-transcriptional control systems for SigH. sigH is expressed as three primary translation products, SigH-sigma(37), SigH-sigma(51), and SigH-sigma(52). In vitro, SigH-sigma(52) was comparable to SigH-sigma(37) in its ability to associate with RNA polymerase core enzyme and specifically initiate transcription in vitro. While SigH-sigma(51/52) were the primary gene products observed throughout early phases of growth, their abundance decreased during later stages in liquid or solid phase cultures while levels of shorter, C-terminally encoded products increased. These included SigH-sigma(37), a product of the downstream translational initiation site, as well as two proteolytic derivatives of SigH-sigma(51/52) (34kDa and 38kDa). Accumulation of SigH-sigma(37) and processing of SigH-sigma(51/52) into these stable 34kDa and 38kDa derivatives correlated with morphological changes on solid medium and physiological maturation in liquid medium. SigH-sigma(51/52) processing did not occur on medium non-permissive for aerial mycelium formation or in one particular developmental mutant (brgA). The proteolytic activity could be detected in vitro using crude extracts of stationary phase cultures, but was absent from exponential phase cultures. prsH, the gene upstream of sigH having sequence similarity to known anti-sigma factors, was able to bind to, and thus presumably inactivate SigH-sigma(52), SigH-sigma(51), and SigH-sigma(37). We have shown elsewhere that prsH was conditionally required for colonial development. Thus, while at least one transcriptional regulator is known to bring about the accumulation of sigH mRNA at different times and different locations in colonies, the post-transcriptional processes described here regulate the activity of different SigH isoforms and program their temporal accumulation pattern, i.e. the elimination of SigH-sigma(51/52) and accumulation of SigH-sigma(37)-like proteins, as a function of development.
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PMID:Post-transcriptional regulation of the Streptomyces coelicolor stress responsive sigma factor, SigH, involves translational control, proteolytic processing, and an anti-sigma factor homolog. 1250 69


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