Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mutation underlying Huntington disease (HD) is CAG expansion in the first exon of the HD gene. In order to investigate the role of CAG expansion in the pathogenesis of HD, we have produced transgenic mice containing the full length human HD cDNA with 44 CAG repeats. By 1 year, these mice have no behavioral abnormalities and morphometric analysis at 6 (one animal) and 9 (two animals) months age revealed no changes. Despite high levels of mRNA expression, there was no evidence of the HD gene product in any of these transgenic mice. In vitro transfection studies indicated that the inclusion of 120 bp of the 5' UTR in the cDNA construct and the presence of a frameshift mutation at nucleotide 2349 prevented expression of the HD cDNA. These findings suggest that the pathogenesis of HD is not mediated through DNA-protein interaction and that presence of the RNA transcript with an expanded CAG repeat is insufficient to cause the disease. Rather, translation of the CAG is crucial for the pathogenesis of HD. In contrast to that seen in humans, the CAG repeat in these mice was remarkably stable in 97 meioses. This suggests that genomic sequences may play a critical role in influencing repeat instability.
Hum Mol Genet 1996 Feb
PMID:Absence of disease phenotype and intergenerational stability of the CAG repeat in transgenic mice expressing the human Huntington disease transcript. 882 73

There are several cell types within the placenta that produce cytokines which can contribute to the regulatory mechanisms that ensure normal pregnancy. The immunological milieu at the maternofetal interface is considered to be crucial for survival of the fetus. Interleukin-2 (IL-2) is expressed by the syncytiotrophoblast, the cell layer between the mother and the fetus. IL-2 appears to be a key factor in maintenance of pregnancy. Therefore, it was important to determine the sequence of human placental interleukin-2. Direct sequencing of human placental IL-2 cDNA was determined for the coding region. Subclone sequencing was carried out for the 5'- and 3'-untranslated regions (5'-UTR and 3'-UTR). The 5'-UTR for human placental IL-2 cDNA is 294 bp, which is 247 nucleotides longer than that reported for cDNA IL-2 derived from T cells. The sequence of the coding region is identical to that reported for T cell IL-2, while sequence analysis of the polymerase chain reaction (PCR) product showed that the cDNA from the 3' end was the same as that reported for cDNA from T cells. Human placental IL-2 cDNA is 1,028 base pairs (excluding the poly A tail), which is 247 bp longer at the 5' end than that reported for IL-2 T cell cDNA. Therefore, the extended 5'-UTR of the placental IL-2 cDNA may be a consequence of alternative promoter utilization in the placenta.
Mol Reprod Dev 1996 Feb
PMID:Sequence of interleukin-2 isolated from human placental poly A+ RNA: possible role in maintenance of fetal allograft. 882 16

The O. aureus estrogen receptor (OaER) gene of 40.4 kb containing ten exons is the first complete piscine gene to be cloned. There are two extra introns: intron I that divides the 5' UTR into two exons, and intron V that intersperses D and E1 exons. Except for I and V, other introns have identical positions to those of human ER gene. All the donor and acceptor splice sites exhibit consensus sequences. The promoter lacks consensus TATA and CAAT boxes. This region exhibits several putative regulatory elements. A functional imperfect ERE deviating at two bases is located in the leader exon, thus suggesting that this gene is autoregulated. The OaER gene lacks an A region whereas its C and E domains are highly conserved. Within the ER subfamily, OaER exhibits the longest F domain of 77 amino acids. OaER has a long 3'UTR constituting >1/2 of its transcript. Using RT-PCR and SI nuclease mapping, we report for the first time the usage of both alternative transcriptional start sites and polyadenylation signals during estrogen-induced OaER expression. Thus, O. aureus may have four species of ER transcripts differing structurally in their transcriptional start sites and lengths of their 3' UTR.
Mol Cell Endocrinol 1996 Jul 01
PMID:The first contiguous estrogen receptor gene from a fish, Oreochromis aureus: evidence for multiple transcripts. 896 90

A screen for Leishmania mexicana genes encoding promastigote-specific flagellar proteins resulted in isolation of genes encoding the major components of the paraflagellar rod. One of these, PFR-2, was characterized extensively. PFR-2 genes are present in the genome as a tandem array of three genes designated PFR-2A, PFR-2B, PFR-2C. PFR-2A and PFR-2B are encoded by a 3.1 transcript while PFR-2C is encoded by a 3.8-kb transcript that has a 3' UTR different from that of the 3.1-kb transcript. Both of these mRNAs were 15-fold more abundant in promastigotes than in amastigotes. Two transcripts immediately upstream of the locus were constitutively expressed while two downstream transcripts were fourfold more abundant in promastigotes than in amastigotes. The PFR genes will provide a good model system for analysis of stage-specific gene regulation in Leishmania as well as assist in the characterization of the function and organization of the paraflagellar rod.
Mol Biochem Parasitol 1996 Oct 01
PMID:Stage-specific expression of the Leishmania mexicana paraflagellar rod protein PFR-2. 889 90

Although encystation and excystation are crucial to transmission of Giardia lamblia, little is known about the regulation of these very distinct differentiation processes. Fingerprinting of giardial mRNA populations throughout the time course of differentiation demonstrated complex patterns in mRNA differential display. Certain transcripts appeared or increased, while others decreased or disappeared at specific times, in response to physiologic stimuli that mimic key stages in parasite descent through the host gastrointestinal tract. This approach has allowed the direct identification of critical stages in differentiation, as well as isolation of genes which may be crucial to the development of G. lamblia. One stage-specific single copy gene (ENC6) whose transcript is greatly upregulated during encystation was analyzed further. Partial sequence analysis revealed no correspondence with known genes. 3'-rapid amplification of cDNA ends (3'-RACE) analysis of ENC6 transcripts at various times of encystation revealed two polyadenylation sites. The more proximal site, 10 nucleotides past the single classic AGTAAA sequence, was utilized only during encystation and its transcript increased approximately 16-fold during the first 24 h of encystation. In contrast, a slightly divergent polyadenylation site 288 nucleotides downstream from the open reading frame (ORF) was used during both vegetative growth and encystation, although its transcript was present at low levels. These studies are the first evidence of differential mRNA processing in G. lamblia and suggest a potential role of the 3'-untranslated region (3'-UTR) in modulating gene expression during differentiation of this primitive eukaryote.
Mol Biochem Parasitol 1996 Oct 18
PMID:Developmentally regulated transcripts and evidence of differential mRNA processing in Giardia lamblia. 889 9

We have shown previously that the mRNA for the growth-associated protein GAP-43 is selectively stabilized during neuronal differentiation. In this study, we explored the role of its highly conserved 3' untranslated region (3'UTR) in mRNA stability and RNA-protein interactions. The 3'UTRs of the rat and chicken GAP-43 mRNAs show 78% sequence identity, which is equivalent to the conservation of their coding regions. In rat PC12 cells stably transfected with the full-length rat or chicken GAP-43 cDNAs, the transgene mRNAs decayed with same half-life of about 3 h. The GAP-43 3'UTR also caused the rabbit beta-globin mRNA to decay with a half-life of 4 h, indicating that the major determinants for GAP-43 mRNA stability are localized in its highly conserved 3'UTR. Three brain cytosolic RNA-binding proteins (molecular mass 40, 65 and 95 kDa) were found to interact with both the rat and chicken GAP-43 mRNAs. These RNA-protein interactions were specific and involved pyrimidine-rich sequences in the 3'UTR. Like the GAP-43 mRNA, the activity of these proteins was enriched in brain and increased during development. We propose that highly conserved pyrimidine-rich sequences in the 3'UTR of this mRNA regulate GAP-43 gene expression via interactions with specific RNA-binding proteins.
Brain Res Mol Brain Res 1996 Mar
PMID:Role of highly conserved pyrimidine-rich sequences in the 3' untranslated region of the GAP-43 mRNA in mRNA stability and RNA-protein interactions. 896 44

Efficient establishment of the symbiosis between rhizobia and their host plants requires precise regulation of bacterial nod genes. The nod gene transcripts in Rhizobium meliloti have approximately 200 nucleotides of untranslated sequence 5' of the start codon (5' UTR). We measured the significance of this region by constructing fusions between deletion derivatives of nodF and the reporter beta-glucuronidase (GUS). Flavonoid-inducible expression of the fusions in R. meliloti was evident when extra copies of the positive transcriptional activators NodD1, NodD3, or SyrM were present. The fusions responded normally over a range of inducer concentrations in Rhizobium leguminosarum bv. trifolii. GUS assays in planta showed no significant difference between the deletion constructs and a wild-type fusion. We conclude that the 5' UTRs of the nod gene transcripts are unlikely to have a significant regulatory role.
Mol Plant Microbe Interact 1996 Dec
PMID:Deletion analysis of the 5' untranslated region of the Rhizobium meliloti nodF gene. 896 36

H19 is an imprinted gene developmentally regulated in man and mouse and implicated in various neoplasms. No corresponding protein product has yet been detected, although several open reading frames (ORFs) could be identified along its RNA. The largest ORF found in the human gene could encode a putative 26 kDa protein. We have isolated two H19 cDNAs (AP and ES) that contain this ORF4 and correspond to incomplete copies of the unique 2.3 kb H19 RNA. In transient expression assays, AP was able to synthesize a 26 kDa protein whereas ES was not. With respect to ORF4, ES exhibits a 536 bp long GC-rich 5' untranslated region, whereas AP contains the last 22 nucleotides of this 5'UTR. Using deletions and point mutations, we have found that the length and probably the secondary structure of the 5'UTR strongly hampers the translatability of the RNA. In addition, a potential role of upstream ORFs (uORFs) was detected as stressed by the enhances translation of a construct mutated in uORF3 overlapping ORF4. Interactions between H19 and proteins are indicated by a specific binding between 5'UTR derived RNA segments and two nuclear proteins of about 27 kDa. Our results favor a potential role of these particular structures and binding properties in general trans-regulation of RNA post-transcriptional processes rather than in normal control of H19 mRNA translation.
Cell Mol Biol (Noisy-le-grand) 1996 Dec
PMID:The 5' part of the human H19 RNA contains cis-acting elements hampering its translatability. 899 20

3T3-L1 preadipocytes ectopically expressing the mammalian RNA-binding protein Hel-N1 expressed up to 10-fold more glucose transporter (GLUT1) protein and exhibited elevated rates of basal glucose uptake. Hel-N1 is a member of the ELAV-like family of proteins associated with the induction and maintenance of differentiation in various species. ELAV proteins are known to bind in vitro to short stretches of uridylates in the 3' untranslated regions (3'UTRs) of unstable mRNAs encoding growth-regulatory proteins involved in transcription and signal transduction. GLUT1 mRNA also contains a large 3'UTR with a U-rich region that binds specifically to Hel-N1 in vitro. Analysis of the altered GLUT1 expression at the translational and posttranscriptional levels suggested a mechanism involving both mRNA stabilization and accelerated formation of translation initiation complexes. These findings are consistent with the hypothesis that the Hel-N1 family of proteins modulate gene expression at the level of mRNA in the cytoplasm.
Mol Cell Biol 1997 Feb
PMID:Ectopic expression of Hel-N1, an RNA-binding protein, increases glucose transporter (GLUT1) expression in 3T3-L1 adipocytes. 900 Dec 49

Previous work from this laboratory [Dompenciel,R.E., Garnepudi,V.R. and Schoenberg,D.R. (1995)J. Biol. Chem.270, 6108-6118] described the purification and properties of an estrogen-regulated endonuclease isolated from Xenopus liver polysomes that is involved in the destabilization of albumin mRNA. The present study mapped cleavages made by this enzyme onto the secondary structure of the portion of albumin mRNA bearing the major cleavage sites. The predominant cleavages occur in the overlapping APyrUGA sequence AUUGACUGA present in a single-stranded loop region, and in AUUGA located within a bulged AU-rich stem. A structural mutation which converted the major loop cleavage site to a hairpin bearing one APyrUGA element eliminated cleavage at the intact site. This confirms that the polysomal RNase is specific for single-stranded RNA. Additional point mutations in the major loop characterized the nucleoside sequence requirements for cleavage. Finally, snake venom exonuclease was used to demonstrate the polysomal RNase generates products with a 3' hydroxyl. Binding of an estrogen-induced protein to a portion of the 3'UTR of vitellogenin mRNA may be involved in its stabilization by estrogen [Dodson,R.E. and Shapiro,D.J. (1994)Mol. Cell. Biol.14, 3130-3138]. The core binding site for this protein bears the sequence APyrUGA, suggesting that stabilization may be accomplished by occlusion of a cleavage site for the polysomal RNase.
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PMID:Cleavage properties of an estrogen-regulated polysomal ribonuclease involved in the destabilization of albumin mRNA. 901 22


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