Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
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Genomic DNA encoding the ovine insulin-like growth factor-I (IGF-I) gene was cloned and sequenced. The predicted amino acid sequence of the mature form of ovine IGF-I was highly homologous to that of human, rat and mouse. Analysis of the DNA sequence between exons 1 and 2 suggested the existence of an alternative 5' exon (exon 1A) and this was confirmed by polymerase chain reaction (PCR) analysis of sheep liver mRNA. Primer extension of mRNA from exon 1A indicated a class of transcripts which initiated at a point 32 nucleotides 5' to the Met codon of exon 1A to give a mRNA comprising exons 1A, 2, 3 and 5. In liver these transcripts co-existed with the alternative exon 1, 2, 3 and 5 mRNA form. Analysis by PCR of the 3' terminus of liver RNA indicated heterogeneity arising from multiple polyadenylation sites; however, of the two possible alternatively spliced 3' exons, only exon 5 could be detected. Expression of IGF-I mRNA, as measured by a solution hybridization/RNase protection assay, predominated in the liver of the neonate and the late-gestation fetus; however, lower levels of expression were seen in multiple tissues throughout fetal and neonatal development.
J Mol Endocrinol 1991 Feb
PMID:The ovine insulin-like growth factor-I gene: characterization, expression and identification of a putative promoter. 201 53

Nerve growth factor (NGF) plays a critical role in the development and survival of neurons in the peripheral nervous system. Following treatment with NGF but not epidermal growth factor, rat pheochromocytoma (PC12) cells undergo neural differentiation. We have cloned a nervous system-specific mRNA, NGF33.1, that is rapidly and relatively selectively induced by treatment of PC12 cells with NGF and basic fibroblast growth factor in comparison with epidermal growth factor. Analysis of the nucleic acid and predicted amino acid sequences of the NGF33.1 cDNA clone suggested that this clone corresponded to the NGF-inducible mRNA called VGF (A. Levi, J. D. Eldridge, and B. M. Paterson, Science 229:393-395, 1985; R. Possenti, J. D. Eldridge, B. M. Paterson, A. Grasso, and A. Levi, EMBO J. 8:2217-2223, 1989). We have used the NGF33.1 cDNA clone to isolate and characterize the VGF gene, and in this paper we report the complete sequence of the VGF gene, including 853 bases of 5' flank revealed TATAA and CCAAT elements, several GC boxes, and a consensus cyclic AMP response element-binding protein binding site. The VGF promoter contains sequences homologous to other NGF-inducible, neuronal promoters. We further show that VGF mRNA is induced in PC12 cells to a greater extent by depolarization and by phorbol-12-myristate-13-acetate treatment than by 8-bromo-cyclic AMP treatment. By Northern (RNA) and RNase protection analysis, VGF mRNA is detectable in embryonic and postnatal central and peripheral nervous tissues but not in a number of nonneural tissues. In the cascade of events which ultimately leads to the neural differentiation of NGF-treated PC12 cells, the VGF gene encodes the most rapidly and selectively regulated, nervous-system specific mRNA yet identified.
Mol Cell Biol 1991 May
PMID:Structure of the gene encoding VGF, a nervous system-specific mRNA that is rapidly and selectively induced by nerve growth factor in PC12 cells. 201 59

Babesia bovis is an intraerythrocytic protozoan that causes bovine babesiosis. Agarose gel electrophoresis of nucleic acids extracted from two isolates of B. bovis reveals, besides bulk DNA, an ethidium bromide-stainable band at about 5.5 kb. Further characterization of the latter with DNase I, RNase and mung bean nuclease suggested it to be a double-stranded RNA. Sonicated parasites were fractionated in a CsCl buoyant density gradient. A sample containing the 5.5-kb RNA was analysed under an electron microscope and a virus-like particle was observed.
Mol Biochem Parasitol 1991 Mar
PMID:A putative RNA virus in Babesia bovis. 205 34

Although the arginine vasopressin (AVP) gene is predominantly expressed in specific hypothalamic neurons, immunoreactive AVP (irAVP) has also been identified in peripheral tissues, including testis. To determine whether hypothalamic and testicular ir-AVPs derive from the same or different transcripts, we examined testicular AVP gene-related transcripts by Northern blot analysis, polymerase chain reaction (PCR), and RNase mapping. We show that the testis contains three distinct AVP gene-related transcripts of 0.67, 0.83, and 2.0 kilobases (kb) which differ in size from the 0.81-kb hypothalamic AVP mRNA. As demonstrated by deadenylation, this size heterogeneity is not due to differences in the length of the poly(A) tails. By the use of exon-specific probes we determined that the 0.67- and the 0.83-kb transcripts contain exons B and C, but not A. In contrast, the 2-kb transcript is the only testicular transcript that contains an exon A-related sequence. By application of the PCR technique, we confirm the existence of testicular transcripts in which exons B and C are spliced together, but exon A is excluded. Our findings indicate that the 0.67- and 0.83-kb mRNA results from a differential splicing event that excludes exon A and that the 2-kb mRNA probably originates from the expression of an AVP-related gene. Since the nonapeptide AVP is encoded by exon A, testicular irAVP cannot arise from the translation of any of the exon B- and C-containing transcripts, and any mRNA that has so far been identified by AVP exon C probes is unrelated to the biosynthesis of AVP-immunoreactive products.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Endocrinol 1991 May
PMID:Novel vasopressin gene-related transcripts in rat testis. 207 24

The 447 male sterility trait in Vicia faba is strictly correlated with the presence of well-defined membranous vesicles or 'cytoplasmic spherical bodies' not found in fertile isogenic maintainer plants, and by the occurrence of a discrete high molecular weight double-stranded RNA. We have purified these cytoplasmic membranous vesicles and find that they contain the dsRNA together with an RNA-dependent RNA polymerase whose activity depends upon the presence of Mg2+, requires the four-nucleoside triphosphates and is unaffected by inhibitors of cellular transcriptases, e.g. alpha-amanitin and Actinomycin D. The dsRNA can be labelled in vitro by incubating the cytoplasmic vesicles with radioactive NTPs, and the RNA synthesized in vitro is also in a double-stranded form as judged by its resistance to RNase digestion at high salt and its behaviour upon CF-11 chromatography. Treatment of the vesicles with a non-ionic detergent releases the dsRNA in the form of a complex with the RNA-dependent RNA polymerase. The enzyme can still carry out the specific synthesis of dsRNA in these solubilized complexes. The cytoplasmic vesicles therefore isolate this vertically transmitted, self-replicating dsRNA from the cellular milieu: the possible mode of action and relevance of this novel genetic element to the 447 cytoplasmic male sterility trait are discussed.
Plant Mol Biol 1990 Apr
PMID:The double-stranded RNA associated with the '447' cytoplasmic male sterility in Vicia faba is packaged together with its replicase in cytoplasmic membranous vesicles. 210 29

Genomic Southern blot analysis of Brassica napus DNA indicates that seed-expressed acyl carrier protein (ACP) is encoded by a multigene family of some 35 genes/haploid genome. Two genomic clones encoding B. napus ACP have been isolated and sequenced. The coding sequences of the 2 respective genes were found to be perfectly homologous to 2 distinct B. napus seed-expressed cDNAs and therefore represent seed-expressed forms of ACP. The 2 genomic ACP sequences share 94% homology within their coding sequences. Both genes are interrupted by 3 intervening sequences whose position within the 2 coding sequences is conserved. RNase protection studies were used to map the transcription start site of one of the genes and to provide further evidence that the gene is seed-expressed. The expression of a sub-group of the ACP gene family was found to be developmentally regulated in concert with the storage lipid synthetic phase of seed development. The coding sequence of both B. napus genes are highly homologous (96% and 93% respectively) to a Brassica campestris ACP cDNA sequence, suggesting that they may have evolved from this ancestral gene.
Plant Mol Biol 1990 Apr
PMID:The isolation and sequence analysis of two seed-expressed acyl carrier protein genes from Brassica napus. 210 33

During the synthesis of fatty acids and their utilization in plastids, fatty acyl moieties are linked to acyl carrier protein (ACP). In contrast to previously cloned organ-specific ACP isoforms, we have now isolated a cDNA clone for a potentially constitutive ACP isoform from a spinach root library. Identity between the amino acid sequence encoded by this cDNA and N-terminal sequence data for ACP-II protein from spinach leaf indicates that the root cDNA encodes ACP-II. The deduced amino acid sequence for ACP-II shows 62% identity with spinach leaf ACP-I. Southern analysis suggests that multiple ACP genes or pseudogenes occur in the spinach genome. High-stringency northern blot analysis and RNase protection studies confirm that, within the region encoding the mature ACP-II, the cloned ACP sequence is expressed in leaves and seeds as well as in roots. Quantitative RNase protection data indicate that the ratio of ACP-I and ACP-II mRNA sequences in leaf is similar to the ratio of the two proteins.
Plant Mol Biol 1990 Nov
PMID:A root acyl carrier protein-II from spinach is also expressed in leaves and seeds. 210 85

The expression of the chloramphenicol-inducible chloramphenicol acetyltransferase gene (cat) of the staphylococcal plasmid pUB112 is regulated at the post-transcriptional level. Previous in vivo analyses suggested that the antibiotic stalls ribosomes that are translating a regulatory leader peptide, and that a stalled ribosome activates the ribosome binding site of the acetyltransferase encoding sequence by opening an attenuating leader mRNA hairpin structure. To test this model, we used a Bacillus subtilis S-30 extract for an in vitro translation system and in vitro synthesized cat in RNAs. We showed that the leader portion of the cat transcript acts as a translational attenuator of cat gene expression in absence of chloramphenicol. The drug stimulates acetyltransferase synthesis by a leader mRNA-dependent activation of translation of the cat message. By using 5' end-labeled transcripts and employing the endogenous RNase activity of the S-30 extract we demonstrated that this activation is due to an antibiotic-induced stalling of a ribosome on cat leader mRNA.
J Mol Biol 1990 Apr 20
PMID:Chloramphenicol-induced translational activation of cat messenger RNA in vitro. 210 1

Overexpression of a family of plasma membrane glycoproteins, known as P-glycoproteins, is commonly associated with multidrug resistance in animal cells. In rodents, three multidrug resistance (mdr or pgp) genes have been identified, but only two can confer the multidrug resistance phenotype upon transfection into animal cells. Using the RNase protection method, we demonstrated that the levels of three mdr gene transcripts differ among mouse tissues, confirming a previous report that the expression of these genes is tissue specific (J.M. Croop, M. Raymond, D. Huber, A. DeVault, R. J. Arceci, P. Gros, and D. E. Housman, Mol. Cell. Biol. 9:1346-1350, 1989). The levels of mdr transcripts were determined for mouse liver tumors spontaneously arising in both C3H/HeN and transgenic animals containing the hepatitis B virus envelope gene and for tumors induced by two different carcinogenic regimens in C57BL/6N and B6C3-F1 mice. The mdr3 gene was overexpressed in all 22 tumors tested. Our results demonstrate that overexpression of the mdr3 gene in mouse liver tumors does not require exposure of the animals to carcinogenic agents and suggest that its overexpression is associated with a general pathway of hepatic tumor development. The overexpression of the mdr3 gene, which is the homolog of human mdr1 gene, in hepatocellular carcinomas may be responsible for the poor response of these tumors to cancer chemotherapeutic agents.
Mol Cell Biol 1990 Nov
PMID:Overexpression of the multidrug resistance gene mdr3 in spontaneous and chemically induced mouse hepatocellular carcinomas. 212 32

To characterize neuronal gene expression in amyotrophic lateral sclerosis (ALS), we quantitated one glial and three neuronal mRNAs in spinal cords of 7 subjects with ALS and 11 controls. The ALS cases showed no loss of mRNA for the neurofilament light subunit when assessed with in situ hybridization. Northern analysis, and RNase protection assay; and no loss of mRNA for amyloid precursor protein or a growth-associated protein (GAP-43/B-50) on Northern analysis. ALS cords also showed no significant change in glial mRNA. Our findings indicate that expression of these neuronal mRNAs is well maintained in ALS-afflicted spinal cord. They do not support the hypothesis of a generalized impairment of neuronal gene transcription in the pathogenesis of this disorder.
Brain Res Mol Brain Res 1990 Jan
PMID:Neuronal gene expression in amyotrophic lateral sclerosis. 215 97


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