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:2.7.7.49 (reverse transcriptase)
31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The paired-homeodomain transcription factor PAX4 is expressed in the developing pancreas and along with PAX6 is required for normal development of the endocrine cells. In the absence of PAX4, the numbers of insulin-producing beta cells and somatostatin-producing delta cells are drastically reduced, while the numbers of glucagon-producing alpha cells are increased. To gain insight into PAX4 function, we cloned a full-length Pax4 cDNA from a beta-cell cDNA library and identified a bipartite consensus DNA binding sequence consisting of a homeodomain binding site separated from a paired domain binding site by 15 nucleotides. The paired half of this consensus sequence has similarities to the PAX6 paired domain consensus binding site, and the two proteins bind to common sequences in several islet genes, although with different relative affinities. When expressed in an alpha-cell line, PAX4 represses transcription through the glucagon or insulin promoters or through an isolated PAX4 binding site. This repression is not simply due to competition with the PAX6 transcriptional activator for the same binding site, since PAX4 fused to the unrelated yeast GAL4 DNA binding domain also represses transcription through the GAL4 binding site in the alpha-cell line and to a lesser degree in beta-cell lines and NIH 3T3 cells. Repressor activity maps to more than one domain within the molecule, although the homeodomain and carboxyl terminus give the strongest repression. PAX4 transcriptional regulation apparently plays a role only early in islet development, since Pax4 mRNA as determined by reverse transcriptase PCR peaks at embryonic day 13.5 in the fetal mouse pancreas and is undetectable in adult islets. In summary, PAX4 can function as a transcriptional repressor and is expressed early in pancreatic development, which may allow it to suppress alpha-cell differentiation and permit beta-cell differentiation.
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PMID:Paired-homeodomain transcription factor PAX4 acts as a transcriptional repressor in early pancreatic development. 1056 52

The Ets variant gene 6 (ETV6/TEL) gene is rearranged in the majority of patients with 12p13 translocations fused to a number of different partners. We present here a case of acute myeloid leukemia M4 with eosinophilia (AML-M4Eo) positive for the CBFb/MYH11 rearrangement and carrying a t(1;12)(q25;p13) that involves the ETV6 gene at 12p13. By 3'rapid amplification of cDNA ends-polymerase chain reaction (3'RACE-PCR), a novel fusion transcript was identified between the ETV6 and the Abelson-related gene (ARG) at 1q25, resulting in a chimeric protein consisting of the HLH oligomerization domain of ETV6 and the SH2, SH3, and protein tyrosine kinase (PTK) domains of ARG. The reciprocal transcript ARG-ETV6 was also detected in the patient RNA by reverse transcriptase-polymerase chain reaction (RT-PCR), although at a lower expression level. The ARG gene encodes for a nonreceptor tyrosine kinase characterized by high homology with c-Abl in the TK, SH2, and SH3 domains. This is the first report on ARG involvement in a human malignancy.
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PMID:The tyrosine kinase abl-related gene ARG is fused to ETV6 in an AML-M4Eo patient with a t(1;12)(q25;p13): molecular cloning of both reciprocal transcripts. 1059 83

An extensive repertoire of protein 4.1R isoforms is predominantly generated by alternative pre-mRNA splicing and differential usage of two translation initiation sites. The usage of the most upstream ATG (ATG-1) generates isoforms containing N-terminal extensions of up to 209 aa compared with those translated from the downstream ATG (ATG-2). To characterize nonerythroid 4.1R proteins translated from ATG-1 and analyze their intracellular localization, we cloned 4.1R cDNAs containing this translation initiation site. Six different clones were isolated from the nucleated human MOLT-4 T-cell line by reverse transcriptase-PCR techniques. Transient expression of the six ATG-1-translated 4.1R isoforms tagged with a c-Myc epitope revealed that all of them predominantly distributed to the plasma membrane and the endoplasmic reticulum. Staining of MOLT-4 cell plasma membranes but not nuclei was also observed by immunofluorescence microscopy by using an antibody specific to the N-terminal extension. Consistent with this, the antibody reacted with a major endogenous protein of approximately 145 kDa present in nonnuclear but absent from nuclear fractions prepared from MOLT-4 cells. Because these data suggested that ATG-1-translated 4.1R isoforms were predominantly excluded from the nucleus, we fused the 209-aa domain to nuclear 4.1R isoforms encoded from ATG-2 and observed that this domain inhibited their nuclear targeting. All these results indicate that the N-terminal domain of ATG-1-translated 4.1R isoforms plays a pivotal role in differential targeting of proteins 4.1R.
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PMID:The N-terminal 209-aa domain of high molecular-weight 4.1R isoforms abrogates 4.1R targeting to the nucleus. 1061 14

Chromosomal analysis of acute monocytic leukemia cells in a female infant revealed a t(6;11)(q27;q23) translocation. Southern blot analysis with a cDNA probe of the MLL gene at chromosome band 11q23 indicated that the breakpoint was in an 8.3-kb BamHI fragment that contained exons 5-11 of the MLL gene. Northern blot analysis showed a faint band corresponding to the MLL chimeric transcript. Structural analysis of a genomic clone with the rearranged MLL gene from der(11) chromosome demonstrated the breakpoint to be localized between exons 6 and 7 of the the MLL gene and to lie in an Alu sequence of this region. The partner gene fused to the 3' part of MLL was shown to be the AF6 gene on chromosome 6q27 by in situ chromosome hybridization and nucleotide sequencing of chimeric MLL cDNA clones. However, it was shown that MLL exon 5 was fused to AF6 in one clone, whereas most clones were MLL exon 6/AF6 chimeric cDNA clones. These findings indicate that exon 6 of MLL is spliced out in the process of transcription in a variant MLL/AF6. In addition, we were able to detect the splicing of exon 6 in either this chimeric MLL/AF6 or MLL transcripts from untranslocated chromosomes by reverse transcriptase-polymerase chain reaction. The detailed genetic map of AF6 was determined by in situ chromosome hybridization and radiation hybrid mapping.
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PMID:Molecular analysis of the rearranged genome and chimeric mRNAs caused by the t(6;11)(q27;q23) chromosome translocation involving MLL in an infant acute monocytic leukemia. 1071 72

ALK (anaplastic lymphoma kinase) is a tyrosine kinase receptor, expressed as part of the chimeric NPM-ALK protein, in anaplastic large cell lymphomas (ALCLs) exhibiting the t(2;5)(p23;q35) translocation. As a result of this translocation, the NPM (nucleophosmin) gene is fused to the portion of the ALK gene encoding its intracytoplasmic segment. In normal mouse tissues, mRNA encoding the Alk receptor has been found only in neural cells, suggesting involvement of this receptor in the development of the nervous system. The purpose of the present study was to examine the presence of ALK transcripts and protein in normal human tissues and a variety of cell lines and human tumors. Emphasis was placed on neuroblastomas because other tyrosine kinase receptors are expressed in human neuroblastomas. Fifty-six cell lines, including 29 lines of neural origin, and lymphoid and nonlymphoid tissue specimens, including 24 neuroblastomas, were investigated for ALK expression, using reverse transcriptase-polymerase chain reaction, Western blotting, and immunohistochemistry. The results confirmed that mRNA encoding ALK protein was not detectable in any normal or neoplastic hematopoietic tissue tested, except for t(2;5)-positive ALCL. The salient finding was that 13 of the 29 cell lines of neural origin and 22 of 24 neuroblastomas were found to express ALK transcripts and ALK protein. However, no correlation was evident between any known prognostic factors and the level of ALK expression.
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PMID:Expression of the ALK tyrosine kinase gene in neuroblastoma. 1079 82

The translocation t(8;16)(p11;p13) is associated with a subtype of acute monocytic leukemia (AML M5) characterized morphologically by erythrophagocytosis and clinically by a poor prognosis. The t(8;16) fuses the MOZ gene from 8p11 with the CBP (also named CREBBP) gene from 16p13. Previously published studies of MOZ and CBP rearrangements in t(8;16)-positive AML have used fluorescence in situ hybridization and Southern blot methodologies, whereas attempts to amplify and to analyze further the chimeric MOZ-CBP and CBP-MOZ transcripts by means of reverse transcriptase-polymerase chain reaction (RT-PCR) have largely been unsuccessful. In the only t(8;16) that has been described at the sequence level using RT-PCR, the CBP-MOZ fusion was found to be out-of-frame, suggesting that the reciprocal MOZ-CBP transcript is the essential one for leukemogenesis. We have developed an RT-PCR strategy that enables us to detect the MOZ-CBP as well as the CBP-MOZ fusions in the two AML M5 with t(8;16)(p11;p13) analyzed. In both leukemias, the combination of a MOZ forward and a CBP reverse primer amplified a strongly expressed 1,128 bp fragment (type I transcript) and a weakly expressed 415 bp fragment (type II transcript). In the type I transcript, nucleotide (nt) 3,745 of MOZ was fused in-frame with nt 284 of CBP, whereas in the type II transcript, nt 3,745 of MOZ was fused out-of-frame with nt 997 of CBP. Nested PCR with a combination of two forward CBP and two reverse MOZ primers amplified CBP-MOZ chimeric transcripts in both cases. Direct sequence analysis showed that nt 283 of CBP was fused in-frame with nt 3,746 of MOZ, that the initiation ATG codon of the CBP gene remained intact, and that there was no mutation or deletion in the part of the CBP gene included in the CBP-MOZ transcript. Thus, the data we present are not informative with regard to the question whether it is the MOZ-CBP or the CBP-MOZ transcript that is leukemogenic. The present RT-PCR method may be of value for rapid identification of the t(8;16) and also for further molecular genetic studies of the two fusion transcripts and their roles in leukemogenesis.
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PMID:RT-PCR analysis of the MOZ-CBP and CBP-MOZ chimeric transcripts in acute myeloid leukemias with t(8;16)(p11;p13). 1086 50

The phytobilin chromophores of phycobiliproteins and phytochromes are biosynthesized from heme in a pathway that begins with the opening of the tetrapyrrole macrocycle of protoheme to form biliverdin IXalpha, in a reaction catalyzed by heme oxygenase. An Arabidopsis thaliana hy1 mutant was previously shown to be deficient in phytochrome responses, and these responses were regained when the plants were administered biliverdin IXalpha. A heme oxygenase-encoding gene, ho1, was recently cloned from the cyanobacterium Synechocystis sp. PCC 6803. When ho1 was expressed in Escherichia coli, the cells produced active ferredoxin-dependent soluble heme oxygenase. The open reading frame of ho1 was fused in frame with a chloroplast transit peptide-encoding sequence from the oli gene of Antirrhinum majus. This construct was placed in a binary plasmid vectorcontaining a kanamycin resistance marker and a cauliflower mosaic virus 35S promoter to control expression of the chimeric oli-ho1 gene and used to transform A. thaliana hy1 plants. Two independent transformed lines were obtained that had the phenotype of the parental Landsberg erecta line and expressed the chimeric gene, as indicated by detection of its mRNA by reverse transcriptase-polymerase chain reaction. The results indicate that Synechocystis sp. PCC 6803 heme oxygenase encoded by ho1 can substitute for the defective HY1 gene product and that the only required enzyme activity of the HY1 gene product is heme oxygenase.
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PMID:Phytobilin biosynthesis: the Synechocystis sp. PCC 6803 heme oxygenase-encoding ho1 gene complements a phytochrome-deficient Arabidopsis thalianna hy1 mutant. 1094 78

Earlier related to parasitic elements, retrotransposons of eukaryotes have been demonstrated to participate in general cell processes such as chromosome repair and evolution of gene expression (Teng et al., 1996; McDonald, 1993). Here, we report the existence of two classes of genomic copies of retrotransposon 1731 with different expression strategies, one of which might be driven by natural selection. The first class uses conventional translational frameshifting known to ensure expression of reverse transcriptase (RT) open reading frame (ORF), depending on the efficiency of frameshifting. The bulk of genomic copies are related to the second class where the frameshift is prevented as a result of the substitution of a rare codon recognising rare tRNA by a codon preferred by host genome, whereas the RT ORF is restored by downstream single nucleotide deletion. We suggest that natural selection has driven the switching of 1731 expression strategy from retrovirus-like to the fusion-ORF expression. This observation is in accordance with the detection in testes of fused Gag-RT polypeptide encoded by 1731. The abundance of RT in testes may serve for normal development of host tissue.
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PMID:Retrotransposon 1731 in Drosophila melanogaster changes retrovirus-like expression strategy in host genome. 1095 99

A semi-nested reverse transcriptase-polymerase chain reaction (RT-PCR) was applied to evaluate the presence of estrogen receptor-alpha (ER-alpha) in human prostate cancer cells. Unexpectedly, a novel fatty acid synthase (FAS)/ER-alpha fusion transcript was identified, in which the N-terminus of FAS was fused in-frame with the C-terminus of ER-alpha. The existence of the FAS/ER-alpha transcript was further confirmed by RT-PCR analysis using various sets of amplification primers and different reverse-transcribed primers in the presence of dimethyl sulfoxide to eliminate the secondary structure of RNA. The predicted FAS/ER-alpha protein would contain largely domain I of FAS and the entire ligand binding domain of ER-alpha. The FAS/ER-alpha was expressed in a variety of human cancer cell lines including prostate, breast, cervical and bladder cancer cell lines. Our data suggest that the presence of FAS/ER-alpha may complicate the FAS and the ER-alpha signalling pathway.
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PMID:Identification of a novel FAS/ER-alpha fusion transcript expressed in human cancer cells. 1101 65

Carnation small viroid-like RNA (CarSV RNA) and its homologous DNA are the two forms of a unique plant retroviroid-like system. CarSV RNA is a 275-nucleotide noninfectious viroid-like RNA, present in certain carnation plants, which can adopt hammerhead structures in both polarity strands and self-cleave accordingly. CarSV DNA is organized as a series of head-to-tail multimers forming part of extrachromosomal elements in which CarSV DNA sequences are fused to sequences of carnation etched ring virus (CERV), a plant pararetrovirus. Analysis of more than 30 CarSV-CERV DNA junctions showed that distinct regions of the viral genome seem able to interact with CarSV DNA. All these junctions were short nucleotide stretches common to both CarSV and CERV DNAs. This suggests a polymerase-driven mechanism for their origin involving an enzyme with low processivity, most likely the viral reverse transcriptase. This view was further supported by the observation that most of CarSV sequences forming part of the junctions correspond either to strong secondary structure motifs in the conformation proposed for CarSV RNA or to its self-cleavage sites, which may have facilitated polymerase jumping. Accompanying the most-abundant CarSV RNA, a series of CarSV RNAs with sequence deletions were previously characterized. Here we have identified some of their corresponding DNA forms, together with other CarSV DNA forms with deletions not found in any CarSV RNA species identified so far. Some of these CarSV DNA forms have also been detected fused to CERV sequences. The existence of these shortened CarSV DNA versions may provide a continuous input of their corresponding transcripts and explain the persistence of CarSV RNAs with defective hammerhead structures for which an RNA-RNA model of amplification seems unlikely.
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PMID:The DNA of a plant retroviroid-like element is fused to different sites in the genome of a plant pararetrovirus and shows multiple forms with sequence deletions. 1104 83


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