Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.48 (transcriptase)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To identify a gene responsible for multiple endocrine neoplasia type 1 (MEN1), we attempted to isolate potentially transcribable fragments from cosmid clones derived from a region on chromosome 11q13 where genetic linkage studies and analyses of loss of heterozygosity in MEN1-associated tumors have localized the MEN1 gene. By an exon-amplification method, we recovered three exon-like sequences from one of these clones, cCI11-367, and using these sequences as probes we were able to isolate new clones from cerebrum, cerebellum, and fetal-liver cDNA libraries. Sequence analysis of these cDNA clones revealed that the transcribed gene, designated ZFM1, encodes a novel 623-amino-acid protein containing domains with interesting structural properties including a nuclear transport domain, a metal binding motif, and glutamine- and proline-rich regions. Analysis by the reverse-transcriptase polymerase chain reaction (RT-PCR) indicated that this gene is expressed in various tissues including endocrine organs such as thyroid gland, pancreas, adrenal gland, and ovary. These data suggest that ZFM1 might be a candidate for mutations that cause MEN1.
Hum Mol Genet 1994 Mar
PMID:Isolation and characterization of a novel gene encoding nuclear protein at a locus (D11S636) tightly linked to multiple endocrine neoplasia type 1 (MEN1). 791 30

RNA preparations from sporulated oocysts of Eimeria nieschulzi were found to contain 2 double-stranded RNA segments of 5.0 kb and 5.7 kb that were not present in other species of Eimeria. Treatment of crude lysates with RNase A revealed that in addition to these two segments, 3 other segments of 0.57 kb, 0.72 kb and 11.5 kb were protected from digestion, suggesting that they were enclosed within particles. Virus-like particles with a diameter of approximately 39 nm were purified by caesium chloride buoyant density centrifugation. Four of the five RNA segments copurified with these particles. In keeping with the nomenclature generally adopted for protozoan viruses, we have named this new isolate ENV 1. The largest RNA segment does not cosediment with ENV 1 particles and may be derived from another RNA-protein complex that is unstable under the conditions used. The particle size and genome structure of ENV 1 both differ from that of the Eimeria stiedae virus (ESV), which is the only other virus to have been isolated from Eimeria to date. Short cDNA clones derived from ENV 1 show significant homology to a region of the Leishmania virus (LRV 1) genome that encodes an RNA-dependent RNA polymerase. The polymerase sequences from ENV 1 and LRV 1 are more closely related to each other than to any other protein sequences in the GenEMBL Database. This raises intriguing questions about the origins of the two viruses, since Eimeria and Leishmania normally infect different hosts and also show different cell tropisms within these hosts.
Mol Biochem Parasitol 1994 Feb
PMID:Virus-like particles in Eimeria nieschulzi are associated with multiple RNA segments. 800 24

Activins, the dimeric polypeptides of inhibin beta-subunits, exhibit paracrine effects on cell proliferation, differentiation, and various other cell functions. The complex biological response to activin appears to involve multiple receptors. In the present study, we examined the isoform mRNA expression of both activin receptor type II (ActR-II) and type IIB (ActR-IIB) genes in mouse reproductive organs, cumulus-oocyte complexes (COCs), and ovulated oocytes. Northern blot analyses of female and male reproductive organs with single-stranded ActR-II cDNA probes revealed that mouse ovaries expressed high levels of the 6.0 kilobase (kb) mRNA, whereas the 3.0 kb transcript was the major mRNA species found in the testis. Reverse transcriptase-polymerase chain reaction (RT-PCR) showed that both COCs and oocytes contained ActR-II mRNA. To examine the expression of ActR-IIB gene, primer selection was made outside the two alternative splicing sites in order to amplify the cDNAs of all four distinct receptor isoforms. The results of RT-PCR demonstrated that isoforms IIB2 and IIB4 were the major mRNA species expressed in both female and male gonads and extragonal reproductive tissues. The ovary expressed all four mRNA isoforms, whereas the testes expressed only three isoforms. whereas the testes expressed only three isoforms. Furthermore, COCs and oocytes contained only the ActR-IIB2 isoform. The differential expression of both activin receptor mRNA isoforms in the reproductive organs suggests that distinct alternative splicing mechanisms are involved in activin receptor gene expression in male and female gonads, and that each of the activin receptors may have its own biological function in reproduction.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Reprod Dev 1994 May
PMID:Expression of activin receptor II and IIB mRNA isoforms in mouse reproductive organs and oocytes. 804 70

Ad4BP, a zinc finger DNA-binding protein, was identified as a transcription factor regulating steroidogenic P-450 genes in a cAMP-dependent manner. Immunochemical and immunohistochemical studies with steroidogenic tissues, adrenal, ovary, and testis, were performed using the antiserum to Ad4BP. Ad4BP was expressed to the same extent in the three zones of the adrenal cortex. Immunohistochemical examination of ovarian follicle and corpus luteum showed the expression of Ad4BP. The granulosa and thecal cells, the two distinct types of the steroidogenic cells in the follicle, gave Ad4BP signals, which were stronger than in the latter cells than in the former. Immunoblot analyses of mature and regressed corpora lutea indicated a parallel expression of Ad4BP and side-chain cleavage P-450, and both proteins significantly decreased in the regressed tissues. Leydig cells surrounding seminiferous tubules gave clear immunostaining signals for Ad4BP. ELP, a mammalian counterpart of Drosophila FTZ-F1 detected in EC cells, and are isoforms transcribed from the same gene. The Ad4BP and ELP forms recognize same nucleotide sequences. Reverse transcriptase-polymerase chain reaction with specific primers for ELP revealed that steroidogenic tissues contained ELP as well as Ad4BP. The effects of the two proteins on the transcription of the CYP11B gene were compared using the expression vectors of Ad4BP and ELP. ELP did not activate transcription and showed a weak inhibitor effect on the Ad4BP-dependent transactivation of the CYP11B gene promoter when transfected simultaneously. A gel shift analysis using in vitro synthesized Ad4BP and ELP revealed that the binding activity of ELP is significantly weaker than that of Ad4BP.
Mol Endocrinol 1994 May
PMID:Functional difference between Ad4BP and ELP, and their distributions in steroidogenic tissues. 805 72

To investigate a potential role of NF2, the gene responsible for hereditary bilateral acoustic neurinomas, during carcinogenesis of non-neurogenic tissues, we screened somatic mutations of NF2 in 55 breast cancers and 44 colorectal carcinomas by an RNase protection assay coupled with the reverse-transcriptase polymerase chain reaction (RT-PCR). By screening the entire coding region of the gene in these tumors, we detected missense mutations in the exon encoding the alpha-helical domain of the NF2 product in two colorectal carcinomas. No mutations were detected in any of the breast cancers. Our results suggested that inactivation of the NF2 gene was associated with carcinogenesis in some, but not the majority of, colorectal tumors. In the course of these analyses, we found various alternatively-spliced forms of NF2 transcript. These variants showed no specificity among the tissues examined except for one that resulted from alternative splicing at the 3'-region; this form was more abundantly expressed in skeletal and cardiac muscles than in other tissues.
Hum Mol Genet 1994 Apr
PMID:Alternative splicing of the NF2 gene and its mutation analysis of breast and colorectal cancers. 806 99

We have cloned the gene encoding the rat serotonin-2 (5-HT2) receptor. The transcription unit is divided into three exons by two introns. The major 5-HT2 transcript is 5.62 kb in length and contains 1173 bases of 5'-untranslated region (5'-UTR) 1413 bases of open reading frame, and 3033 bases of 3'-UTR. Primer extension demonstrates one strong transcription initiation site 1173 nt from the start codon. Reverse transcriptase-polymerase chain reaction analysis indicates the presence of at least one additional minor site of transcription initiation 1355 nt from the start codon. There are ATA boxes 28 nt 5' to both the major and minor sites of transcription initiation. Functional promoter mapping was carried out in a transient transfection assay. This analysis reveals that there are negative attenuating elements between 2.5 and 2.3 kb from the initiation site and positive elements between 1100 and 200 nt from transcription initiation. Minimal promoter sequences are contained within 200 nt of the major site of transcription initiation. These findings suggest that the expression of the 5-HT2 receptor gene is regulated by a combination of positive and negative elements operating through the minimal promoter.
Mol Cell Neurosci 1994 Jun
PMID:Cloning and functional promoter mapping of the rat serotonin-2 receptor gene. 808 27

Recent studies have identified a new family of inwardly rectifying K+ channels, members of which are known by the acronyms ROMK1, IRK1, and GIRK1. We have isolated cDNAs encoding the human homologue of ROMK1 from an adult kidney cDNA library. The sequences of the human kidney ROMK1 cDNA clones indicated that they were derived from at least two types of mRNAs, human ROMK1A and human ROMK1B, differing in sequence at their 5' ends. The isolation of the human ROMK1 gene, localized to chromosome band 11q24 by fluorescence in situ hybridization, indicated that the different ROMK1 transcripts were generated by alternative splicing. Human ROMK1A mRNA was predicted to encode a protein of 389 amino acids, having 93% identity with the 391-residue rat ROMK1 protein, and expression studies in Xenopus oocytes indicated that it encoded a Ba(2+)-sensitive inwardly rectifying K+ channel with properties similar to those reported for cloned rat ROMK1. Human ROMK1B mRNA was predicted to encode a protein of 372 amino acids whose sequence was truncated at the amino terminus but otherwise identical to that of the human ROMK1A protein. Translation of human ROMK1B mRNA was predicted to initiate at a codon corresponding to Met-18 of human ROMK1A mRNA. Reverse transcriptase-polymerase chain reaction amplification of human kidney mRNA revealed human ROMK1A and -B transcripts as well as a third type of transcript, human ROMK1C mRNA, which was predicted to encode a protein identical to human ROMK1B. Human ROMK1A, -B, and -C transcripts were identified in kidney, whereas only human ROMK1A mRNA could be detected in pancreatic islets and other tissues in which human ROMK1 was expressed at low levels. Thus, tissue-specific alternative splicing of human ROMK1 mRNA may result in the expression of a family of ROMK1 proteins.
Mol Pharmacol 1994 May
PMID:Alternative splicing of human inwardly rectifying K+ channel ROMK1 mRNA. 819 Jan 2

Birnaviruses typically encode a polyprotein that is the precursor to the structural proteins of the virus and a protein of rare abundance, VP1, that is the putative dsRNA replicase and/or transcriptase. We have reconstructed the VP1 gene of IBDV from a library of cDNA clones and expressed the gene in Escherichia coli and in Saccharomyces cerevisiae. We could not detect an RNA polymerase activity associated with E. coli-derived VP1, and neither could we promote the yeast-derived VP1 to replicate exogenous IBDV dsRNA. However, the yeast-derived VP1 was shown to have an actinomycin-insensitive RNA polymerase activity that can recognise an endogenous template in S. cerevisiae. Our work suggests that further studies on birnavirus replication may be best addressed using an S. cerevisiae expression system.
Biochem Mol Biol Int 1993 Aug
PMID:Expression and RNA dependent RNA polymerase activity of birnavirus VP1 protein in bacteria and yeast. 822 Feb 61

Despite the rapid mutational change that is typical of positive-strand RNA viruses, enzymes mediating the replication and expression of virus genomes contain arrays of conserved sequence motifs. Proteins with such motifs include RNA-dependent RNA polymerase, putative RNA helicase, chymotrypsin-like and papain-like proteases, and methyltransferases. The genes for these proteins form partially conserved modules in large subsets of viruses. A concept of the virus genome as a relatively evolutionarily stable "core" of housekeeping genes accompanied by a much more flexible "shell" consisting mostly of genes coding for virion components and various accessory proteins is discussed. Shuffling of the "shell" genes including genome reorganization and recombination between remote groups of viruses is considered to be one of the major factors of virus evolution. Multiple alignments for the conserved viral proteins were constructed and used to generate the respective phylogenetic trees. Based primarily on the tentative phylogeny for the RNA-dependent RNA polymerase, which is the only universally conserved protein of positive-strand RNA viruses, three large classes of viruses, each consisting of distinct smaller divisions, were delineated. A strong correlation was observed between this grouping and the tentative phylogenies for the other conserved proteins as well as the arrangement of genes encoding these proteins in the virus genome. A comparable correlation with the polymerase phylogeny was not found for genes encoding virion components or for genome expression strategies. It is surmised that several types of arrangement of the "shell" genes as well as basic mechanisms of expression could have evolved independently in different evolutionary lineages. The grouping revealed by phylogenetic analysis may provide the basis for revision of virus classification, and phylogenetic taxonomy of positive-strand RNA viruses is outlined. Some of the phylogenetically derived divisions of positive-strand RNA viruses also include double-stranded RNA viruses, indicating that in certain cases the type of genome nucleic acid may not be a reliable taxonomic criterion for viruses. Hypothetical evolutionary scenarios for positive-strand RNA viruses are proposed. It is hypothesized that all positive-strand RNA viruses and some related double-stranded RNA viruses could have evolved from a common ancestor virus that contained genes for RNA-dependent RNA polymerase, a chymotrypsin-related protease that also functioned as the capsid protein, and possibly an RNA helicase.
Crit Rev Biochem Mol Biol 1993
PMID:Evolution and taxonomy of positive-strand RNA viruses: implications of comparative analysis of amino acid sequences. 826 9

R1 and R2 are retrotransposable elements that integrate at specific sites in the 28S ribosomal RNA (rRNA) genes of Bombyx mori and Drosophila melanogaster. We have previously shown that most insect species contain insertions in their 28S genes at the R1 and/or R2 site. We have sequenced the 3' half of R1 and R2 elements from three additional insect species: the fungus gnat, Sciara coprophila (Diptera); the Japanese beetle, Popillia japonica (Colleoptera); and the parasitic wasp, Nasonia vitripennis (Hymenoptera). The elements were obtained by screening lambda phage genomic clones containing rDNA units and by a polymerase chain reaction approach using degenerate primers to conserved sequences in the reverse-transcriptase domain, in combination with a second primer to the 28S gene 3' of the insertion site. Comparisons of the sequences of R1 and R2 from four insect orders suggest that the organization of their open-reading frames has been conserved and is therefore likely to be similar throughout insects. This sequence analysis also indicates that, except for 5' truncations generated during the retrotransposition process itself, most elements have not accumulated mutations that would make them inactive. Popillia japonica and N. vitripennis differed from previously described species, in that (a) P. japonica contained multiple families of R2 and (b) N. vitripennis contained multiple families of R1. Nucleotide sequence identity between these different families is low. Amino acid sequence identity of their open-reading frames averaged only 41% for the R2 families of P. japonica and 35% for the R1 families of N. vitripennis. The presence of multiple highly divergent families of elements within a species suggests either that each insertion family is able to maintain its copy number without eliminating the other families in its competition for a limited number of 28S genes or that there has been extensive horizontal transfer of R1 and R2 elements between insect species.
Mol Biol Evol 1993 Jan
PMID:Sequence relationship of retrotransposable elements R1 and R2 within and between divergent insect species. 838 93


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