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:3.1.27.1 (RNase)
16,360 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The m1 receptor is one of five muscarinic receptors that mediate the metabotropic actions of acetylcholine in the nervous system where it is expressed predominantly in the telencephalon and autonomic ganglia. RNase protection, primer extension, and 5'-rapid amplification of cDNA ends analysis of a rat cosmid clone containing the entire m1 gene demonstrated that the rat m1 gene consists of a single 657-base pairs (bp) non-coding exon separated by a 13. 5-kilobase (kb) intron from a 2.54-kb coding exon that contains the entire open reading frame. The splice acceptor for the coding exon starting at -71 bp relative to the adenine of the initiating methionine. This genomic structure is similar to that of the m4 gene (Wood, I. C., Roopra, A., Harrington, C. A., and Buckley, N. J. (1995) J. Biol. Chem. 270, 30933-30940 and Wood, I. C., Roopra, A., and Buckley, N. J. (1996) J. Biol. Chem. 271, 14221-14225). Like the m4 gene, the m1 promoter lacks TATA and CAAT consensus motifs, and the first exon and 5'-flanking region are not gc-rich. The 5'-flanking region also contains the consensus regulatory elements Sp-1, NZF-1, AP-1, AP-2, E-box, NFkappaB, and Oct-1. Unike the m4 promoter, there is no evidence of a RE1/NRSE silencer element in the m1 promoter. Deletional analysis and transient transfection assays demonstrates that reporter constructs containing 0.9 kb of 5'-flanking sequence and the first exon are sufficient to drive cell-specific expression of reporter gene in IMR32 neuroblastoma cells while remaining silent in 3T3 fibrobasts.
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PMID:Structure of the m1 muscarinic acetylcholine receptor gene and its promoter. 920 29

Stromelysin-1, matrix metalloproteinase-3 (MMP-3), is an important endopeptidase selectively expressed by somatic cells in organ tissues. The renal tubulointerstitium, for example, comprises tubular epithelium and interstitial fibroblasts forming the principal mass of the kidney. We observed that mRNA encoding stromelysin-1 is detectable in murine renal fibroblasts, but not in proximal tubular epithelium. Transcripts measured by RNase protection assay in renal fibroblasts increase following exposure to phorbol ester, and thereafter, activated stromelysin-1 protein can be detected in culture media by Western blotting. A 6.4 Kb genomic clone containing the putative stromelysin-1 promoter was isolated and a relevant 2.1 Kb PstI restriction fragment including 2.1 Kb of the immediate 5'-flanking region was sequenced on both strands. Two transcriptional start sites were identified by primer extension; the major start site corresponded to a previously established position in the rat promoter, and a second undescribed minor transcriptional start site was located 16 bp upstream of the primary site. A HiNF-A chromatin-activating element at -106 bp was found in the early promoter region of pR336 and an active AP-1 site at -72 bp with an Ets/PEA-3 motif at -203 bp was suggested by transient transfection of luciferase minigenes into renal fibroblasts responsive to phorbol ester. This Ets element was identical to a site in the early promoter of the fibroblast-specific gene FSP1. A baseline enhancement in activity of pR336 in fibroblasts was further observed with the addition of 5' flanking sequence out to -1980 bp. This additional region of flanking sequence contains two modular regions: one of multiple PEA-3 elements between -684 bp and -1955 bp and a second region between -1929 bp and -1980 bps containing a second AP-1 site at -1929 bp, a MBF-1/ MEP-1 metal binding site, and a PPAR peroxisome proliferator element at -1950 bp. Our findings implicate a gene structure with expected activity in a mesenchymal phenotype. The PKC-dependent regulation of the stromelysin-1 gene supports the notion that it may be modulated during inflammation or tissue remodeling.
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PMID:Identification of promoter activity and differential expression of transcripts encoding the murine stromelysin-1 gene in renal cells. 921 54

The c-fos and c-jun mRNA expressions were measured by the RNase protection assay method following intraperitoneal injection of haloperidol, (D1 and D2 receptor antagonists), (-)-sulpiride, (D2 receptor antagonist), and SCH23390, (D1 receptor antagonist). Haloperidol and (-)-sulpiride increased their mRNA expressions in a dose-dependent manner, peaking at 30 min after injection followed by a gradual decline. The SCH23390 did not induce expression of either c-fos or c-jun mRNA. A significant decrease of c-fos as well as c-jun mRNA expression was found due to pretreatment with SCH23390 (1 mg/kg i.p.) followed by injection of (-)-sulpiride (20 mg/kg i.p.). The results suggest that the expression of these mRNAs is closely related to the dopamine D2-like antagonism. Administration of haloperidol or (-)-sulpiride increased AP-1 DNA binding activity with similar manner of dose-dependence, whereas their activities were reduced by Fos and Jun antibodies, implying that AP-1 components, transcriptional factors, forming due to Fos and Jun were actually activated by either haloperidol or (-)-sulpiride.
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PMID:The comparative effects of haloperidol, (-)-sulpiride, and SCH23390 on c-fos and c-jun mRNA expressions, and AP-1 DNA binding activity. 921 76

The adhesive proteins in the desmosome type of cell junction consist of two members of the cadherin superfamily, the desmogleins and desmocollins. Both desmogleins and desmocollins occur as at least three different isoforms with various patterns of expression. The molecular mechanisms controlling the differential expression of the desmosomal cadherin isoforms are not yet known. We have begun an investigation of desmoglein gene expression by cloning and analysing the promoters of the human genes coding for the type 1 and type 3 desmogleins (DSG1 and DSG3). The type 1 isoform is restricted to the suprabasal layers of the epidermis and is the autoantigen in the autoimmune blistering skin disease pemphigus foliaceous. The type 3 desmoglein isoform is also expressed in the epidermis, but in lower layers than the type 1 isoform, and is the autoantigen in pemphigus vulgaris. Phage lambda genomic clones were obtained containing 4.2 kb upstream of the translation start site of DSG1 and 517 bp upstream of the DSG3 start site. Sequencing of 660 bp upstream of DSG1 and 517 bp upstream of DSG3 revealed that there was no obvious TATA box, but a possible CAAT box was present at -238 in DSG1 and at -193 in DSG3 relative to the translation start site. Primer extension analysis and RNase protection experiments revealed four putative transcription initiation sites for DSG1 at positions -163, -151, -148 and -141, and seven closely linked sites for DSG3, the longest being at -140 relative to the translation start site. The sequences at these possible sites at -166 to -159 in DSG1 (TTCAGTCC) and at -124 to -117 in DSG3 (CTTAGACT) have some similarity to the initiator sequence (CTCANTCT) described for a TATA-less promoter often from -3 to +5, and the true transcription initiator site might therefore be the A residue in these sequences. There were two regions of similarity between the DSG1 and DSG3 promoters just upstream of the transcription initiation sites, of 20 and 13 bp, separated by 41 bp in DSG1 and 36 bp in DSG3. The significance of these regions of similarity remains to be elucidated, but the results suggest that they represent a point at which these two desmoglein genes are co-ordinately regulated. Analysis of the upstream sequences revealed GC-rich regions and consensus binding sites for transcription factors including AP-1 and AP-2. Exon boundaries were conserved compared with the classical cadherin E-cadherin, but the equivalent of the second cadherin intron was lacking. A 4.2 kb region of the human DSG1 promoter sequence was linked to the lacZ gene reporter gene in such a way that there was only one translation start site, and this construct was used to generate transgenic mice. We present the first transgenic analysis of a promoter region taken from a desmosomal cadherin gene. Our results suggest that the 4.2 kb upstream region of DSG1 does not contain all the regulatory elements necessary for correct expression of this gene but might have elements that regulate activity during hair growth.
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PMID:Characterization of the regulatory regions in the human desmoglein genes encoding the pemphigus foliaceous and pemphigus vulgaris antigens. 940 90

AP19 is the smallest polypeptide component of AP-1, the clathrin associated protein complex found in clathrin-coated vesicles of the Golgi apparatus. Two genomic clones that encode homologues of AP19 were isolated from Arabidopsis thaliana (AAP19-1 and AAP19-2). Analysis of their nucleotide sequences predict proteins of 162 and 163 amino acids with mr of 18,913 and 18,758 respectively. Amino acid sequence comparisons with mammalian, yeast and plant clathrin associated sequences indicates that the Arabidopsis genes encode polypeptides that are more closely related to the AP19 proteins associated with clathrin-coated Golgi vesicles than to AP17, which is part of the AP-2 complex of endocytic clathrin-coated pits. Ribonuclease protection assays showed that both genes are expressed in all Arabidopsis tissues throughout development. Constitutive transcription of AAP19-1 was confirmed in transgenic Arabidopsis seedlings and plants containing an AAP19-1 promoter::beta-glucuronidase (GUS) fusion by ribonuclease protection assays and GUS histochemical staining.
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PMID:Molecular characterization of the AP19 gene family in Arabidopsis thaliana: components of the Golgi AP-1 clathrin assembly protein complex. 942 6

UDP-glucuronosyltransferase UGT1A7 catalyzes the glucuronidation of benzo(a)pyrene metabolites and other bulky aromatic compounds. Both UGT1A7 mRNA and an associated enzyme activity (benzo(a)pyrene7, 8-dihydrodioltransferase activity) are markedly increased in livers of rats treated with beta-naphthoflavone or 4-methyl-5-pyrazinyl-3H-1,2-dithiole-3-thione (oltipraz). Nuclear runoff assays show that the effects of both inducers are primarily due to transcriptional activation. A 27-kilobase region that included the UGT1A7/UGT1A6 promoter regions was cloned. Primer extension and RNase protection studies indicated >/=30 transcription start sites in five clusters between bases -85 and -40 respective to the translation start codon. There was no recognizable TATA box, but the promoter region is TA-rich. Sequence analysis revealed potential binding sites for CCAAT enhancer-binding protein, activator protein 1, and hepatic nuclear factors 1, 3, and 4, but no xenobiotic response elements or antioxidant response elements, implicated in the regulation of other genes by beta-naphthoflavone or oltipraz, were found. A UGT1A7 gene reporter plasmid directed strong constitutive expression in transient transfection assays using primary rat hepatocytes. Treatment with 3-methylcholanthrene or oltipraz had no effect compared with similarly treated pGL3-Basic-transfected cells. These results suggest that the regulatory elements controlling xenobiotic inducibility of UGT1A7 transcription are located either 5' or 3' of bases -1600 to +54. One possibility is that the polycyclic aromatic-mediated regulation of UGT1A7 occurs via the xenobiotic response element flanking the UGT1A6 locus 7 kilobase pairs downstream.
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PMID:Transcriptional activation of the UDP-glucuronosyltransferase 1A7 gene in rat liver by aryl hydrocarbon receptor ligands and oltipraz. 948 89

Multiple variant alleles of the human arylamine N-acetyltransferase genes, NAT1* and NAT2*, alter the capacity of individuals to metabolize arylamines by N-acetylation. Although biochemical and genetic studies have improved our understanding of the molecular basis of the acetylation polymorphism in humans and other mammals, regulation of NAT* gene expression is not understood. In the present study, a segment of the 5'-untranslated region of mouse Nat2* was sequenced and characterized. Primer extension analysis and RNase protection assays exposed multiple transcription initiation sites located 112 to 151 bases upstream of the translational start site. Computer sequence analysis revealed a promoter-like region located within the region 530 bases upstream of the translational start site consisting of TATA boxes, upstream promoter elements such as a CAAT box and Sp1 binding site, regulatory elements such as a palindromic hormone response element (HRE), and enhancer regions such as an AP-1 transcription factor binding site. Transient expression of CAT reporter constructs of the mouse Nat2*-palindromic HRE demonstrated positive regulation of the HSV-thymidine kinase 1 (tk1) promoter and induced the expression of chloramphenicol acetyltransferase (CAT). This induction was initiated by the addition of hormones such as 5alpha-dihydrotestosterone (DHT) or dexamethasone and was entirely dependent on the presence of androgen or glucocorticoid receptors, respectively. Together with recent discoveries regarding the effects of testosterone on the expression of Nat2* in mouse kidney during development, the findings reported in this article suggest that the HRE found in the promoter region of Nat2* is a potential candidate for the mediation of androgenic regulation of Nat2* in mouse kidney.
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PMID:Characterization of a hormone response element in the mouse N-acetyltransferase 2 (Nat2*) promoter. 957 94

The Tie-2 receptor plays a key role in vascular development, although little is known about the factors controlling its expression. Here we report the first cloning and characterisation of the 5' regulatory region of human tie-2. Multiple transcription start sites were identified between -414 and -265 bp upstream of the start codon using 5' RACE, fluorescent primer extension, and RNase protection assays. The human tie-2 promoter contains several transcription factor-binding sequences including ets, SP-1, AP-1, and GATA-1, but there are no canonical TATA or CCAAT initiation sequences proximal to the transcription start sites. Human tie-2 reporter constructs demonstrated approximately 10-fold greater activity in endothelial cells compared with fibroblasts. In endothelial cells the tie-2 promoter exhibited 5 and 16% of the activity of human tie-1 (830 bp) and KDR (1.1 kb) promoters, respectively. This promoter will be a useful tool for studying factors that regulate tie-2 expression and targeting the vasculature.
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PMID:Cloning and partial characterization of the human tie-2 receptor tyrosine kinase gene promoter. 983 43

Five subtypes of the muscarinic receptor have been cloned from both the rat and human genomes. Although all five genes have the coding sequences in a single exon, their structures 5' of the initiation codon are largely uncharacterized, except for the M4 receptor. In the brain, muscarinic receptors mediate motor and memory function by interaction with their ligand acetylcholine. In addition, the M1 muscarinic subtype has been implicated in behavior, stress-adaptive cardiovascular reflexes, and blood pressure regulation. In the current study the M1 muscarinic receptor noncoding 5'-flanking region has been identified and characterized, including the promoter and two 5' noncoding exons located approximately 13-14 kb from the coding exon. Similar to the M4 muscarinic receptor gene the M1 promoter is GC-rich, contains no TATA box, but has two potential CAAT boxes and several putative binding sites for transcription factors such as SP1 and AP-1-3. The transcription initiation site was identified by RNase protection and primer extension. Promoter activity was confirmed in transient expression assays, using luciferase reporter constructs. A 0.89-kb fragment consisting of 480 bp of the promoter, exon 1, and part of intron 1 expressed luciferase activity in two M1 receptor-expressing cell lines (CCL-107 and CCL-147), whereas a longer fragment (1.5 kb) that extends into intron 2 demonstrated significantly increased luciferase activity. The constructs exhibited responses indicating the presence of functional glucocorticoid-, acute-phase-, and heat shock-responsive elements.
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PMID:Identification and characterization of the rat M1 muscarinic receptor promoter. 1003 60

The reduced folate carrier (rfc1) gene encodes a protein that is involved in the intracellular accumulation of folates. Point mutations in this gene and alterations resulting in the down regulation of its message are major factors involved in the resistance to antifolate chemotherapeutic compounds. As a framework for understanding the significance of such changes in relation to gene expression and function, in this report we describe the organization of the rfc gene from human lymphoblasts. The gene contains 5 exons (2 to 6) coding for protein. At least four 5' exons, used in a mutually exclusive manner in the production of the rfc message from lymphoblast cells, are spliced to exon 2, which contains the translational start site. "Semi-quantitative" PCR indicates that exon 1 is preferentially used. The major transcriptional start site has been mapped by RACE and RNase protection to a region 109 to 135 base pairs 5' to the start of exon 1. The 5' region of the gene has no TATA box-like sequence but contains several consensus binding sites for transcriptional factors such as SP-1, MZF1, CREB, AP-1, ETS, GATA-1 and GATA-2. The overall organization of the human gene is similar to that of the hamster and mouse genes.
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PMID:Structural organization of the human reduced folate carrier gene: evidence for 5' heterogeneity in lymphoblast mRNA. 1022 52


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