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)

We have previously shown (K. Kas et al, Nat. Genet., 15: 170-174, 1997) that the developmentally regulated zinc finger gene pleomorphic adenoma gene 1 (PLAG1) is the target gene in 8q12 in pleomorphic adenomas of the salivary glands with t(3;8)(p21;q12) translocations. The t(3;8) results in promoter swapping between PLAG1 and the constitutively expressed gene for beta-catenin (CTNNB1), leading to activation of PLAG1 expression and reduced expression of CTNNB1. Here we have studied the expression of PLAG1 by Northern blot analysis in 47 primary benign and malignant human tumors with or without cytogenetic abnormalities of 8q12. Overexpression of PLAG1 was found in 23 tumors (49%). Thirteen of 17 pleomorphic adenomas with a normal karyotype and 5 of 10 with 12q13-15 abnormalities overexpressed PLAG1, which demonstrates that PLAG1 activation is a frequent event in adenomas irrespective of karyotype. In contrast, PLAG1 was overexpressed in only 2 of 11 malignant salivary gland tumors analyzed, which suggests that, at least in salivary gland tumors, PLAG1 activation preferentially occurs in benign tumors. PLAG1 over-expression was also found in three of nine mesenchymal tumors, i.e., in two uterine leiomyomas and one leiomyosarcoma. RNase protection, rapid amplification of 5'-cDNA ends (5'-RACE), and reverse transcription-PCR analyses of five adenomas with a normal karyotype revealed fusion transcripts in three tumors. Nucleotide sequence analysis of these showed that they contained fusions between PLAG1 and CTNNB1 (one case) or PLAG1 and a novel fusion partner gene, i.e., the gene encoding the transcription elongation factor SII (two cases). The fusions occurred in the 5' noncoding region of PLAG1, leading to exchange of regulatory control elements and, as a consequence, activation of PLAG1 gene expression. Because all of the cases had grossly normal karyotypes, the rearrangements must result from cryptic rearrangements. The results suggest that in addition to chromosomal translocations and cryptic rearrangements, PLAG1 may also be activated by mutations or indirect mechanisms. Our findings establish a conserved mechanism of PLAG1 activation in salivary gland tumors with and without 8q12 aberrations, which indicates that such activation is a frequent event in these tumors.
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PMID:Conserved mechanism of PLAG1 activation in salivary gland tumors with and without chromosome 8q12 abnormalities: identification of SII as a new fusion partner gene. 1002 85

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

The mitochondrial genome of Plasmodium falciparum encodes highly fragmented rRNAs. Twenty small RNAs which are putative rRNA fragments have been found and 15 of them have been identified as corresponding to specific regions of rRNA sequence. To investigate the possible interactions between the fragmented rRNAs in the ribosome, we have mapped the ends of many of the small transcripts using primer extension and RNase protection analysis. Results obtained from these studies revealed that some of the rRNA transcripts were longer than the sequences which encode them. To investigate these size discrepancies, we performed 3' RACE PCR analysis and RNase H mapping. These analyses revealed non-encoded oligo(A) tails on some but not all of these small rRNAs. The approximate length of the oligo(A) tail appears to be transcript-specific, with some rRNAs consistently showing longer oligo(A) tails than others. The oligoadenylation of the rRNAs may provide a buffer zone against 3' exonucleolytic attack, thereby preserving the encoded sequences necessary for secondary structure interactions in the ribosome.
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PMID:The fragmented mitochondrial ribosomal RNAs of Plasmodium falciparum have short A tails. 1032 33

GC factor (GCF) was reported as a transcriptional regulator that binds to specific GC-rich sequences in the epidermal growth factor receptor (EGFR) gene promotor, repressing its transcription (Kageyama R. and Pastan I. Cell, 59: 815-825, 1989). In this paper, the author presents revisions of the cDNA and the amino acid sequences of the GCF. 1) 5' rapid amplification of cDNA end (5'RACE) for analysis of RNA of a cancer cell line, A431, was performed, which revealed that the 5' end of GCF cDNA was fused to a 308 bp fragment of other cDNA; simultaneously, the real 5' end cDNA sequence with 31 bp was identified. RNase protection assay presented a main protected band, which was consistent with the result of the RACE analysis. 2) T at the position 787 of the previously reported GCF cDNA was absent from RT-PCR on A431 total RNA. 3) A new sequence with 114 bp was observed on A431 RNA between the positions 851 and 852 of the already reported cDNA by RT-PCR. These observations were confirmed by RT-PCR analyses of RNAs prepared from several other human cell lines, including a non-transformed one (HFL), and white blood cells derived from a normal person. 4) Sequence of genomic GCF DNA was consistent with the new cDNA sequence but not with the previously reported one. 5) The remaining sequence of GCF cDNA was found to be identical to that of the previously reported GCF, based on the results of RT-PCR analyses of RNA prepared from human white blood cells. 6) By the corrections, the GCF cDNA consisted of 2661 bp nucleotides. This revised GCF cDNA (the wild type) encodes a protein of 781 amino acids, including two new sequence regions of 186 amino acids on the N-terminal side of this protein. The revisions eliminated the highly basic region of the amino-terminus of the previously reported GCF, while the other three fourth amino acid sequences of the GCF protein that contained leucine-zipper-like domain had not changed. The revised GCF had no highly homologous protein in the database except the previously reported GCF. 7) The author has developed a specific antibody to human GCF protein. This antibody specifically recognized a protein with a molecular weight of approximately 100 kDa present in the extracts from human cell lines, as confirmed by immunoprecipitation followed by Western blotting. 8) Indirect immunofluorescence of A431 and HeLa cells using the anti-GCF antibody showed that the GCF protein was localized in the nucleus, suggesting that the revised GCF is a nucleoprotein.
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PMID:[Revisions of the cDNA and primary protein structure of human transcription factor GCF]. 1048 38

Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that encodes a small conductance cAMP-activated chloride ion channel. In the CF pancreatic duct, mutations in CFTR cause a reduction in bicarbonate secretion. This is thought to result from CFTR operating in parallel with a chloride-bicarbonate (Cl(-)/HCO(-)(3)) exchanger, located in the apical membrane of pancreatic duct cells. The molecular basis of this Cl(-)/HCO(-)(3) exchanger has not been identified. A combination of screening cDNA libraries, RNase protection, and 5' RACE analysis was used to identify Cl(-)/HCO(-)(3) exchangers in human fetal pancreas. An AE2 Cl(-)/HCO(-)(3) exchanger was shown to be expressed in human fetal pancreas from the midtrimester of gestation, at a time when CF-associated pathology commences. In addition, an AE1 Cl(-)/HCO(3) was identified in fetal pancreas but was absent from the adult pancreas and cultured ductal epithelial cells from fetal and adult pancreas.
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PMID:Chloride-bicarbonate exchangers in the human fetal pancreas. 1049 Dec 90

Endothelin-converting enzyme-1 (ECE-1) mRNA is expressed in three isoforms, termed a, b, and c, originating from alternative promoters. In cultured bovine aortic endothelial cells, we detected mRNA isoform expression of ECE-1a and ECE-1b/c, respectively. Investigating transcriptional mechanisms of bovine endothelial ECE-1a expression in more detail, we identified multiple transcription start sites localized 120-415 nucleotides upstream from the presumptive translation start codon by RNase protection assay and 5' RACE. Using luciferase reporter gene assays we found that 1.4 kb of the 5' untranslated region showed strong promoter activity in endothelial cells. Sequence analysis revealed 71% overall homology of the bovine ECE-1a promoter with its human homologue. The proximal 680 base pair promoter region was shown to contain cis elements that are sufficient for basal and serum-induced transcriptional activation.
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PMID:Cloning and functional characterization of the bovine endothelin-converting enzyme-1a promoter. 1052 9

Gamma-aminobutyric acid (GABA) type A receptors are multisubunit ligand-gated ion channels which mediate inhibition in the brain. The GABA(A) receptor alpha3 subunit gene exhibits extensive variation in its developmental and regional expression, but the detailed mechanisms governing the expression patterns of this gene remain unknown. We have cloned and begun to characterize the murine alpha3 subunit gene Gabra3. All but one of the 10 exons and the intron-exon boundaries have been sequenced; the first intron is in the 5' untranslated region (5'UTR) of the alpha3 mRNA. Rapid amplification of the cDNA 5'-end (5'-RACE) and RNase protection indicated many transcription start sites, with the major site (=+1) corresponding to a 5'UTR of 178 bases. Most sites were in or just downstream of a region of 55 (mouse) and 25 (human) GA repeats in the proximal promoter, as revealed by genome walking of Gabra3 and the human gene GABRA3. No canonical TATA or CAAT boxes or initiator (Inr) sites were found in either promoter, but both contained conserved consensus sites for several transcription factors. Progressive deletion of the mouse promoter produced positive or negative effects on expression of reporter (luciferase) constructs, with the highest observed activity in several types of transiently transfected cells for a construct containing bases -320 to +35. The GA repeats and a much shorter nearby series of four GC repeats, the first three of which are part of a consensus E2F site, appear to contribute significantly to mouse promoter activity. Upstream GA repeats enhanced activity of the SV40 promoter, and the GA repeat sequence bound nuclear proteins from several tissues.
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PMID:The mouse GABA(A) receptor alpha3 subunit gene and promoter. 1058 10

Human ECE-1 is expressed in four isoforms with different tissue distribution and its mRNA and protein levels are altered under certain pathophysiological conditions. To investigate the transcriptional regulation of ECE-1, we studied the regulatory region of ECE-1c, the major ECE-1 isoform. A genomic clone comprising the complete human ECE-1 gene including the putative ECE-1c-specific promoter was obtained. Up to 968 bp upstream of the putative c-specific translation initiation start codon and several serial deletion mutants were subcloned into a reporter vector and transfected into endothelial (BAEC, EA.hy926, ECV304) and epithelial (MDA MB435S, MCF7) cells, showing very strong promoter activity in comparison to the SV40 promoter and to the previously described ECE-1a and 1b promoters. Transfection of serial deletion mutants indicated two positive regulatory regions within the promoter (-142/-240 and -240/490) likely involved in binding GATA and ETS transcription factors. RNase protection assay (RPA) and 5'-RACE revealed multiple transcriptional start sites located at about -110, -140 and -350 bp. Site-directed mutagenesis demonstrated a crucial role for the E2F cis-element for basal ECE-1c promoter activity. Additionally, we found a correlation between isoform-specific ECE-1 mRNA levels and corresponding ECE-1a, 1b, 1c promoter activities.
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PMID:Characterization of the c-specific promoter of the gene encoding human endothelin-converting enzyme-1 (ECE-1). 1068 50

The murine gastrin-releasing peptide receptor (mGRP-R) is a member of the G protein-coupled receptor family and mediates important physiological actions of its specific ligand, the gastrointestinal hormone/neurotransmitter GRP, including mitogenic properties in the mouse Swiss 3T3 fibroblasts. Glucocorticoids and increases in intracellular cAMP are reported to alter GRP-R gene transcription, but the molecular basis for these effects is unknown. To begin to identify possible gene regulatory mechanisms that are responsible for modifying mGRP-R expression, we determined its structure and investigated its basal promoter activity. We isolated and characterized genomic bacteriophage P1 clones encoding the mouse gastrin-releasing peptide receptor (mGRP-R). By DNA sequencing and Southern blot analyses, we determined the protein coding region to be contained in three exons interrupted by two introns 20 and 2kb in length. The open reading frame of the putative GRP-R gene encodes for a 384-amino-acid protein which demonstrates 48% identity with the mouse BRS-3 protein and 53% identity with the mouse NMB-R protein. The mGRP-R gene locus extends over 29kb and was mapped to the X-chromosome (DXMit20) utilizing a minisatellite polymorphism in the 5' UTR and by fluorescent in-situ hybridization (FISH). In Swiss 3T3 cells, which natively express mGRP-R, two gene-specific mRNA species of 3 and 7kb can be detected by Northern blot analysis. With RNase protection assays, and independently with inverse PCR of 5' RACE clones, common mRNA initiation sites were identified clustered between 21 and 61bp downstream of a TTTAAA motif, which is located 450bp upstream of the ATG translation start site. However, different polyadenylation sites are utilized. A 2kb genomic DNA fragment extending from 2147 to 141 bases 5' to the ATG translation start was cloned into a luciferase reporter plasmid and shown to contain promoter activity in Swiss 3T3 and COS-7 cells. Progressive promoter truncations and mutations of a cyclic AMP response element (CRE) located 83bp upstream of the TTTAAA motif demonstrate that transcriptional mGRP-R activation in Swiss 3T3 cells only occurs when both the TTTAAA motif and the intact CRE site are retained. With the availability of the full structure of the mGRP-R gene and the minimal promoter sequences reported in this study, it will be possible in future studies to investigate the molecular basis for transcriptional regulation of the mGRP-R gene by glucocorticoids, cAMP and other factors.
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PMID:Molecular organization of the mouse gastrin-releasing peptide receptor gene and its promoter. 1068 96

Two overlapping clones encoding for a ribonuclease from six-day-old larvae of the insect Ceratitis capitata (Cc-RNase) have been isolated by immunoscreening a cDNA library and by 5' RACE. The sequence of the Cc-RNase cDNA contains an open reading frame of 414 nucleotides encoding for a precursor protein of 138 amino acids long with a putative signal peptide consisting of 19 amino acids. The calculated M(r) of the mature protein was found to be 13.7 kDa. Multiple alignments of the deduced amino acid Cc-RNase sequence with other ribonucleases revealed an approximate 25% average identity. Despite the low percentage of identity, histidine and lysine residues which are essential for its catalytic activity, were found to be completely conserved. Furthermore, expression of the clone in E. coli resulted in the production of a recombinant product that showed strong immunoreactivity with anti-RNase specific antibodies. These results support the hypothesis that the identified clone encodes for a protein which is a new member of the RNase superfamily.
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PMID:Isolation and sequencing of a cDNA encoding for a ribonuclease from the insect Ceratitis capitata. 1069 91


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