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)

Under conditions unfavorable to growth, the nematode Caenorhabditis elegans enters a developmentally arrested stage, the dauer larva. We have examined gene expression in the dauer larva and during recovery from the dauer stage. Run-on transcription assays with isolated nuclei reveal a depression of general RNA polymerase II transcription to 11-17% of that in other stages. Transcription of individual gene families (including actin, collagen, hsp70, and histone) is similarly depressed relative to actively growing stages. Dauer larvae are, however, capable of being induced for heat shock messages, indicating that they are competent to initiate and elongate transcripts. For most genes surveyed, reduced transcription in dauer larvae correlates with a decrease in message abundance. Hsp70 mRNA, however, is transcribed at lower rates but accumulates at levels comparable to those in other stages. Interestingly, dauer larvae are 15-fold enriched in a mRNA for a C. elegans hsp90 gene. Hsp90 mRNA accumulation is regulated at least in part by differential stability. Dauer larvae thus appear to have a unique pattern of gene expression. Upon placement in food, dauer larvae reenter the developmental pathway as late-stage larvae. Dauer recovery is accompanied by a temporally regulated sequence of gene expression. At least four distinct patterns of gene expression can be distinguished during exit from the dauer stage. Steady-state levels of hsp70 and polyubiquitin mRNA rise sharply within 75 min of recovery before declining by the fourth hour. Actin and histone mRNAs increase steadily following 2-4 hr of recovery, whereas myosin mRNA increases after 10 hr. In contrast, hsp90 mRNA declines sharply within the first 75 min of recovery. Changes in mRNA populations during dauer formation and exit may be physiologically relevant.
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PMID:Gene expression in the Caenorhabditis elegans dauer larva: developmental regulation of Hsp90 and other genes. 157 99

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.
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PMID:IgM anti-Fc gamma R autoantibodies trigger neutrophil degranulation. 182 27

Insulin-like growth factor-I (IGF-I) has anabolic effects on skeletal tissues, acting as both a systemic hormone and an autocrine/paracrine regulator of cellular function. We have previously reported that estradiol (E2) stimulation of rat osteoblast proliferation in vitro was inhibited by IGF-I antibodies. We show here that E2, similar to IGF-I, also increases alpha 1(I) procollagen mRNA levels in primary cultures of rat calvarial osteoblasts. The E2 effect on collagen mRNA lags behind that produced by recombinant IGF-I by about 12 h and was also abolished in the presence of cycloheximide or by the addition of antibodies against IGF-I. Furthermore, 17 beta E2 induced a 2- to 2.5-fold elevation of the level of IGF-I mRNA within 2-4 h, which persisted thereafter. The E2 stimulation of IGF-I mRNA was not blocked by cycloheximide, suggesting that de novo protein synthesis of an intermediate protein was not required. The IGF-I mRNA half-life, estimated by treating the cells with the RNA polymerase inhibitor 5,6-dichloro-1 beta-D-ribofuranosylbenzimidazole, was about 7 h and was not altered by E2 treatment. On the other hand, nuclear run-on assays indicated that E2 increased the transcriptional activity of the IGF-I gene, and this effect was further enhanced in cells overexpressing E2 receptors after transient transfection. These findings suggest that IGF-I may serve as a mediator for the anabolic effects of E2 on bone, and that E2 stimulates IGF-I gene expression at least in part through transcriptional control.
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PMID:Estradiol regulation of insulin-like growth factor-I expression in osteoblastic cells: evidence for transcriptional control. 194 4

Collagen mRNA synthesis in HeLa cells was evaluated by in vitro transcription of type I collagen DNA, nuclear run-on studies, and steady-state mRNA analysis. Type I collagen mRNA was accurately initiated by HeLa cell RNA polymerase II in nuclear extracts, and run-on analysis indicted that mRNAs for collagen types alpha 1(I), alpha 2(I), alpha 1(III), alpha 1(IV), and alpha 2(V) were synthesized in HeLa cells. However, on assessing the steady-state levels of mRNAs of collagen types alpha 1(I), alpha 2(I), alpha 1(IV), and alpha 2(V), no type I mRNA was found in HeLa cells while types alpha 1(IV) and alpha 2(V) collagen mRNAs were observed. These results suggest that a postinitiation process prevents the accumulation of type I collagen mRNAs in HeLa cells. Persistence of types IV and V collagen mRNAs is consistent with the involvement of types IV and V collagen in adhesion of HeLa cells to glass or plastic.
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PMID:Genes for collagen types I, IV, and V are transcribed in HeLa cells but a postinitiation block prevents the accumulation of type I mRNA. 198 7

Two genomic sequences that share homology with Rp11215, the gene encoding the largest subunit of RNA polymerase II in Drosophila melanogaster, have been isolated from the nematode Caenorhabditis elegans. One of these sequences was physically mapped on chromosome IV within a region deleted by the deficiency mDf4, 25 kilobases (kb) from the left deficiency breakpoint. This position corresponds to ama-1 (resistance to alpha-amanitin), a gene shown previously to encode a subunit of RNA polymerase II. Northern (RNA) blotting and DNA sequencing revealed that ama-1 spans 10 kb, is punctuated by 11 introns, and encodes a 5.9-kb mRNA. A cDNA clone was isolated and partially sequenced to confirm the 3' end and several splice junctions. Analysis of the inferred 1,859-residue ama-1 product showed considerable identity with the largest subunit of RNAP II from other organisms, including the presence of a zinc finger motif near the amino terminus, and a carboxyl-terminal domain of 42 tandemly reiterated heptamers with the consensus Tyr Ser Pro Thr Ser Pro Ser. The latter domain was found to be encoded by four exons. In addition, the sequence oriented ama-1 transcription with respect to the genetic map. The second C. elegans sequence detected with the Drosophila probe, named rpc-1, was found to encode a 4.8-kb transcript and hybridized strongly to the gene encoding the largest subunit of RNA polymerase III from yeast, implicating rpc-1 as encoding the analogous peptide in the nematode. By contrast with ama-1, rpc-1 was not deleted by mDf4 or larger deficiencies examined, indicating that these genes are no closer than 150 kb. Genes flanking ama-1, including two collagen genes, also have been identified.
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PMID:Molecular cloning and sequencing of ama-1, the gene encoding the largest subunit of Caenorhabditis elegans RNA polymerase II. 258 13

Collagens are a structurally and functionally heterogenous group of proteins encoded by a family of genes that share evolutionary history. Collagen gene expression is regulated both in developmental, tissue-specific manners as well as in response to a variety of biologic and pharmacologic inducers. In the present review we have attempted to synthesize a conceptual overview of the available information from studies aimed at deciphering the molecular mechanisms of collagen gene expression. We have chosen to focus our discussion mainly, although not exclusively, to observations relating to type I collagen gene for a number of practical reasons. The underlying theme that emerges from this survey of the literature is that the regulation of collagen gene expression is complex, utilizing transcriptional, posttranscriptional and translational mechanisms. Although the transcriptional control mechanisms that involve activation and modulation of collagen gene transcription by RNA polymerase II appear to predominate, preferential stabilization of collagen mRNAs and modulation of translational discrimination appear to play significant roles in the regulation of collagen biosynthesis under some physiological situations. Molecular organization of the regulatory regions of collagen genes reveal a mosaic of subdomains with overlapping sequence motifs, involved in positive and negative transcriptional regulation. The precise identity of the cis-acting subdomains of the promoter/enhancer-proximal DNA of collagen gene and how they interact with the trans-acting nuclear protein(s) have yet to be elucidated and will remain the focus of future studies.
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PMID:Molecular mechanisms of collagen gene expression. 266 48

Mutations in the Caenorhabditis elegans dpy-13 (dumpy) gene result in a short, chunky body shape. This gene was tagged by insertion of the Tc1 transposon, and the wild-type gene was cloned by chromosomal walking 11 kb from ama-1, a cloned gene encoding the large subunit of RNA polymerase II. Three transposon insertion sites in dpy-13 are located near the 5' end of a 1.2 kb transcribed region. The EMS-induced reference allele, dpy-13(e184), carries a small deletion near the middle of this gene. The DNA sequence reveals that dpy-13 is a member of the collagen multi-gene family, and it could encode a polypeptide of 302 amino acids. A 146 base pair sequence, encoding amino acids 56-103, is unique in the C. elegans genome, and it hybridizes to a 1 kb mRNA of moderate abundance.
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PMID:dpy-13: a nematode collagen gene that affects body shape. 284 84

Mov13 mice carry a single Moloney murine leukaemia virus (M-MuLV) proviral copy in the first intron of the alpha 1(I) collagen gene. Virus insertion interferes with the synthesis of stable alpha 1(I) collagen messenger RNA and causes a recessive lethal mutation. The virus insertion has induced changes of the methylation pattern as well as the chromatin conformation in the mutated gene. Specifically, a DNase-hypersensitive site which is associated with active transcription of the wild-type collagen gene is not present in the mutant allele. The block of collagen expression could be caused by virus-induced instability of collagen mRNA or by impaired initiation of transcription. To distinguish between these possibilities, we have compared the activity of the alpha 1(I) collagen gene promoter in cell lines derived from wild-type and Mov13 embryos by nuclear run-on transcription experiments and S1 mapping of nuclear RNA. We show here that initiation of transcription of the mutant gene is reduced 20-100-fold. This indicates that the virus-induced change of chromatin structure in the promoter region of the mutant gene prevents RNA polymerase from binding to its DNA template. Our results are consistent with the notion that the promoter-associated DNase-hypersensitive site is a prerequisite for rather than a consequence of gene activity.
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PMID:Retrovirus insertion inactivates mouse alpha 1(I) collagen gene by blocking initiation of transcription. 396 Jan 20

The precise location of the 3' ends of the chicken pro alpha 2(I) collagen gene have been identified by S1 nuclease protection of overlapping genomic fragments by calvaria poly A containing RNA and size determination of the protected fragments on DNA sequencing gels. The gene ends 300 and 306 bp and 754 and 777 bp from the translation stop codon. The two sets of ends explain the major and minor pro alpha 2(I) collagen mRNAs previously observed, which may result from either RNA polymerase readthrough of the first termination site and/or different processing sites.
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PMID:Multiple 3' ends of the chicken pro alpha 2(I) collagen gene. 619 84

Chick genomic DNA containing the extreme 5' end of the alpha 2 (type I) collagen gene has been used as template in an in vitro HeLa cell transcription system. RNA polymerase II-dependent transcription initiates from a specific site on this DNA. The precise location of this site was determined by three types of experiments: sizing of in vitro-synthesized RNA runoff transcripts, comparing the sequence of the in vitro-made RNA transcripts with the structure of the DNA template, and identifying the first and second nucleotides of the in vitro-synthesized transcripts. Transcription was found to initiate 33 base pairs downstream from a canonical Goldberg-Hogness sequence (TATAAATA). This in vitro start site is the same as the initiation site of in vivo-synthesized collagen RNA.
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PMID:Accurate in vitro transcriptional initiation of the chick alpha 2 (Type I) collagen gene. 627 Jan 47


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