Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.27.5 (RNase)
 17,967 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The CD7 molecule is a differentiation antigen found on the surface of T lymphocytes and also on a very minor fraction of acute nonlymphocytic leukemia (ANLL). To study the genomic structure of the CD7 gene, two clones (SY4 and SY22) were isolated by screening a genomic library with a CD7 cDNA probe. Restriction mapping of these two phage clones showed that both overlapped each other, covering a total length of 23 kilobases (kb). Transfection of mouse L cells demonstrated that SY22 contains the gene expressing the CD7 antigen reactive with monoclonal CD7 antibody (Tp40), while SY4 does not. Subcloning of a 10.5 kb fragment from a 14.4 kb insert of SY22 contained the structural gene for the CD7 antigen. Detailed restriction mapping and partial sequence analysis revealed the CD7 gene to consist of four exons. By RNase protection assay, multiple initiation sites -122 base pairs (bp) to -38 bp from ATG translation initiation site were demonstrated. The promoter region had high G + C content and contained two SP1 binding sites (CCGCCC) and an AP2 binding site (CCCCAGGC), but lacked CAAT and TATA motifs.
 ...
PMID:Molecular cloning of the gene coding for the human T cell differentiation antigen CD7. 171 Oct 9

Overlapping murine genomic DNA fragments containing the entire cDNA sequence were isolated from a cosmid library prepared from the DBA/2J strain of mice. The gene is more than 80-kb long, consisting of 16 exons. All of the exon-intron boundaries have been defined. The organization of the gene is highly conserved between the murine and human genes at least for the several exons and introns for which information for the human gene is available [Morreau et al., J. Biol. Chem. 264:20655, 1989]. Primer extension and RNase protection experiments indicated the presence of three potential transcription initiation sites, which are preceded by GC-rich SP1 binding sites but without typical TATA or CAT boxes, as is often the case for genes coding for housekeeping proteins. Compared to the cDNA sequence from C57BL/6J mouse, there were five nucleotide polymorphisms in the protein-coding region, two of which resulted in altered amino acids.
 ...
PMID:Organization of the mouse acid beta-galactosidase gene. 190 71

We have isolated genomic clones that contain the promoter region of the rat IGF-I receptor gene. A unique transcriptional start site was suggested by the results of primer extension and RNase protection assays, which also defined a 940-base 5'-untranslated region. Despite the single start site, the proximal 415 base pairs of 5'-flanking region were devoid of TATA or CCAAT elements. The region surrounding the start site was, however, similar to a recently described "initiator" sequence that can direct specific transcription initiation in the absence of a TATA element. The 5'-flanking region was GC-rich and contained several possible SP1 sites, but also included potential ETF and AP-2 binding sites. The rat IGF-I receptor gene promoter region appears to have some sequences similar to both "housekeeping" and highly regulated promoters and may be an example of an intermediary class of regulatory region.
 ...
PMID:Cloning and characterization of the proximal promoter region of the rat insulin-like growth factor I (IGF-I) receptor gene. 216 25

Regulation of human immunodeficiency virus (HIV) gene expression is dependent on specific regulatory regions in the long terminal repeat. These regions include the enhancer, SP1, "TATA," and trans-activating (TAR) regions. In addition, viral regulatory proteins such as tat and rev are important in regulating HIV gene expression. The mechanism of tat activation remains the subject of investigation, but effects at both transcriptional and posttranscriptional levels seem likely. Previous mutagenesis of the tat protein revealed that the amino terminus, the cysteine-rich domain, and the basic domain were all required for complete tat activation. Mutants of other viral trans-acting regulatory proteins, including E1A, tax, and VM65, have been identified that were capable of antagonizing the activity of their corresponding wild-type proteins. We wished to determine whether mutants of the tat protein could be identified that exhibited a similar phenotype. One mutant (delta tat) that truncated the basic domain of tat resulted in a transdominant phenotype inhibiting tat-induced gene expression of the HIV long terminal repeat but not other viral promoters. This mutant exhibited its maximal phenotype in cotransfection experiments when present in an 8- to 30-fold molar excess over the wild-type tat gene. Trans-activation of the HIV long terminal repeat by delta tat was very defective at the DNA concentrations used in these experiments. RNase protection analysis indicated that this mutant decreased tat-induced steady-state mRNA levels of the HIV long terminal repeat. Second-site mutations of the delta tat gene in either the amino terminus or cysteine region eliminated the transdominant phenotype. In contrast to tat, which was localized predominantly to the nucleolus, delta tat was present in both the nucleus and cytoplasm, suggesting that it may inhibit tat function by preventing nucleolar localization. Transdominant mutants of tat may have a role in potentially inhibiting HIV gene expression.
 ...
PMID:A transdominant tat mutant that inhibits tat-induced gene expression from the human immunodeficiency virus long terminal repeat. 219 47

In order to clarify the transcriptional regulation of the NFKB2 gene (lyt-10, NF-kappa Bp100), we have characterized the structure and function of its promoter regions. Based on the nucleotide sequence of cDNA clones and the 5' flanking genomic region of the NFKB2 gene, RT-PCR analysis in a number of human cell lines demonstrated the presence of two alternative noncoding first exons (1a and 1b). Two distinct promoter regions, P1 and P2, were identified upstream of each exon, containing multiple sites of transcription initiation, as shown by RNase protection analysis. Sequence analysis of these regions showed a CAAT box upstream of exon 1a and high G-C content regions within both P1 and P2. Consensus binding sites for transcription factors, including SP1, AP1 and putative NF-kappa B (kappa B sites), were found upstream of each exon. In particular, six kappa B sites were identified, all but one of them capable of binding NF-kappa B complexes in vitro. Transfection in HeLa cells of plasmids containing P1 and P2 sequences linked to a chloramphenicol acetyltransferase reporter gene indicated that both P1 and P2 can act independently as promoters. Co-transfection of NF-kappa B effector plasmids (NF-kappa Bp52 and RelA) with a reporter gene linked to P1 and P2 showed that the NFKB2 promoter regions are regulated by NF-kappa B factors. RelA transactivates the NFKB2 promoter in a dose-dependent manner, whereas NF-kappa Bp52 acts as a repressor, indicating that the NFKB2 gene may be under the control of a negative feedback regulatory circuit.
 ...
PMID:Structural and functional characterization of the promoter regions of the NFKB2 gene. 754 12

The TTG-2 gene has been identified at the site of chromosomal translocations in acute T-cell leukemia's (T-ALL). These breakpoints map to a region between 2 and 30 kb upstream of TTG-2 in chromosome 11p13. To establish the role of these translocation breakpoints in the deregulation of TTG-2 in T-ALL we have determined the complete structure of this gene. Isolation of new TTG-2 cDNA clones from fetal liver identified an alternative transcript (TTG-2a) containing two new noncoding 5' exons. Analysis of exon/intron boundaries, identified 6 exons spread over 35 kb in 11p13. The gene encodes two alternative transcripts initiating from two promoters. TTG-2a, from promoter 1 (P1) and TTG-2b, from promoter 2 (P2) differ in the length of the 5' untranslated region, but encode the same protein. A high level of TTG-2a was present in fetal liver and spleen, whereas in adult kidney a low level of TTG-2a and a high level of TTG-2b was found. The transcription start site for TTG-2a was identified by RNase protection experiments and it displayed sequence homology to an initiator element (inr). P1 lacks a TATA box, but binding sites for SP1 and GATA-1 are present. This new genomic organisation revealed that all known chromosomal translocations map upstream of P2, removing P1 and putative upstream regulatory sequences leaving P2 intact. These results show that chromosomal translocations disrupt the TTG-2 gene itself, further confirming its role in the development of T-ALL.
 ...
PMID:The TTG-2/RBTN2 T cell oncogene encodes two alternative transcripts from two promoters: the distal promoter is removed by most 11p13 translocations in acute T cell leukaemia's (T-ALL). 773 86

Multiple alternatively spliced 5' untranslated regions (5'UTRs) have been identified in growth hormone (GH) receptor mRNA isolated from hepatic and adipocyte tissue. In the present study, the preferential utilisation of a GC-rich 5'UTR, designated exon 1B, was observed following the isolation of ovine (o) GH receptor cDNA clones from a skeletal muscle cDNA library. Although exon 1B-oGH receptor mRNA was expressed in all tissues examined, marked differences in the level of expression relative to the whole GH receptor transcript pool were observed between tissues. A single genomic clone (lambda 9) was isolated that encompassed exon 1B, together with 6 kilobase pairs of 5' and 12 kilobase pairs of 3' flanking sequence. Multiple transcription initiation sites were identified using RNase protection analysis on skeletal muscle poly(A)+ RNA, a result consistent with the absence of a proximal TATA box element. A CAAT box (-37 to -33) and a putative binding site for SP1 (a GC box -68 to -63) were found in the sense orientation immediately upstream of major transcription initiation site. Transfection of a series of overlapping promoter fragments linked to the luciferase reporter gene into HuH7, CHO and HeLa cells defined a core promoter element of 134 base pairs that was sufficient for maximum promoter activity. The emerging complexity of the 5' regulatory region of the GH receptor gene was emphasised by the observation that probes derived from exon 1B and the distal 3' intron boundary do not hybridise with previously cloned genomic sequences that span the liver-specific P1 promoter and exon 2.
 ...
PMID:Differential expression of growth hormone receptor messenger RNA from a second promoter. 775 37

The murine manganous superoxide dismutase-encoding gene (MnSOD) is highly homologous in both sequence and organization to its rat homolog. MnSOD is encoded by five exons spanning approx. 7 kb of DNA. RNA blot analysis indicated multiple RNA species, with the major RNA corresponding to a 960-bp message. This major transcript is highly inducible by tumor necrosis factor (TNF) in murine fibroblasts. Analysis of other murine tissues demonstrated ubiquitous expression. RNase protection and primer extension assays used to map the 5' end of the gene revealed a series of closely spaced multiple transcription start points. Sequence analysis of the 1.7 kb of 5' flanking DNA showed high homology to the 5' proximal 950 bp of the rat homolog. Within this region, multiple potential regulatory elements are present, including several SP1 sites, two NF kappa B sites and an antioxidant-response element. However, no TATA box was identified, placing MnSOD in the family of inducible genes that lack consensus TATA-box elements and contain G+C-rich promoter regions.
 ...
PMID:Cloning and characterization of the murine manganous superoxide dismutase-encoding gene. 787 82

The human MDR3 (or MDR2) P-glycoprotein is probably involved in the transport of phospholipids from liver hepatocytes into bile (Smit et al. (1993) Cell 75, 451-462). In accordance with this function, MDR3 is highly expressed in human liver, but lower mRNA levels were also found in adrenal, heart, muscle and cells of the B-cell compartment. We have cloned and analyzed the MDR3 promoter region. It is GC-rich, and contains neither a TATA nor a CAAT box, but it does contain multiple putative SP1 binding sites, features also found in so-called housekeeping genes. RNase protection and primer extension analyses indicate that the MDR3 gene has multiple transcription start sites in a GC-rich region with considerable homology to the putative mouse mdr2 promoter. A 3 kb genomic fragment containing the MDR3 start sites directs transcription of a chloramphenicol acetyltransferase (CAT) reporter gene upon transient transfection in the human hepatoma cell line HepG2. This transcription is orientation dependent, and stimulated by a SV40 enhancer, indicating that the 3 kb insert contains the core promoter elements of the MDR3 gene. The promoter region contains several consensus sequences where known or putative liver-specific (C/EBP, HNF5) or lymphoid specific (Pu.1, ets-1) transcription factors may bind.
 ...
PMID:Characterization of the promoter region of the human MDR3 P-glycoprotein gene. 789 60

The retinoblastoma gene (RB1) is a recessive oncogene implicated in a number of human tumors. Although the RB1 gene is expressed in most proliferating cells, there is considerable evidence for the transcriptional regulation of this gene. Therefore, we have performed a detailed analysis of the regulatory elements in the promoter of the human RB1 gene. Deletion analysis of the 5' upstream region determined the location of the basal promoter to be between -208 and -179 nucleotides relative to the translational start. This region contains essential binding sites for the transcription elements ATF and SP1 and potentially important sites for E2F and steroid hormone responsiveness but no TATA or CAAT boxes. Primer extension and RNase protection analysis identified two initiation sites at -176 and -128 base pairs, both downstream of the promoter. Cotransfection experiments revealed repression of the RB1 promoter by its protein product p110RB1. This repression has been mapped to the core promoter region containing the E2F-binding site; however, this site is not required for autorepression.
 ...
PMID:Characterization of the human RB1 promoter and of elements involved in transcriptional regulation. 804 53


1 2 3 Next >>