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Query: UNIPROT:P06889 (Mol)
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Crithidia fasciculata proteins p18 and p17 are associated with kinetoplast DNA and are encoded by genes KAP2 and KAP3, respectively. Polymerase chain reaction (PCR) amplification using primers within the coding sequences of each gene revealed that the KAP2 and KAP3 genes are linked on the same chromosomal DNA and are separated by a 1.8 kb intergenic region containing several long homopolymer tracts. The KAP2 gene has a 3'UTR of more than 1.1 kb or almost three times as long as the KAP2 coding sequence. Several restriction enzyme polymorphisms in this region of the chromosome are the result of sequence differences between the two alleles of the KAP2 gene. The predicted amino-acid sequences of alleles KAP2-1 and KAP2-2 differ by three non-conservative amino acid substitutions in the highly basic carboxyl tail of the protein and suggest that the protein products could have different physical and biological properties. The KAP2 and KAP3 genes have different patterns of mRNA expression during the cell cycle with the KAP3 transcript varying periodically during the cell cycle in the same manner as transcripts of several kinetoplast and nuclear DNA replication genes.
Mol Biochem Parasitol 1997 Oct
PMID:Tandem arrangement of two genes encoding kinetoplast-associated H1 histone-like proteins. 929 99

Changes in endothelial nitric oxide synthase (eNOS) expression may be involved in the endothelium-dependent vasorelaxation dysfunction associated with several vascular diseases. In the present work, we demonstrate that eNOS mRNA contains a previously undescribed cis element in the 3' untranslated region (3' UTR). A U+C-rich segment in the 3' UTR is critical in complex formation with bovine aortic endothelial cell cytosolic proteins. Tumor necrosis factor alpha (TNF-alpha), which destabilizes eNOS mRNA, increased the binding activity of the cytosolic proteins in a time-dependent manner. These data suggest that endothelial cytosolic proteins bind to the 3' UTR of eNOS mRNA. These proteins may play a role in TNF-alpha-induced eNOS mRNA destabilization.
Mol Cell Biol 1997 Oct
PMID:Endothelial cytosolic proteins bind to the 3' untranslated region of endothelial nitric oxide synthase mRNA: regulation by tumor necrosis factor alpha. 1289 3

Fragile X mental retardation syndrome is associated with an expansion of a CGG repeat within the 5'UTR of the first exon of the FMR1 gene, abnormal methylation of the CpG island in the promoter region, and a transcriptional silencing of this gene. We studied transcriptional regulation of the FMR1 gene using protein footprint analysis of the active and inactive gene in vivo . We identified four footprints within the FMR1 promoter region which correspond to consensus binding sites of known transcription factors, alpha-PAL/NRF1, Sp1, H4TF1/Sp1-like and c-myc. These footprints were present in normal cells with a transcriptionally active FMR1 gene. The same footprints were present in different cell types: primary fibroblasts, lymphoblastoid cells and peripheral lymphocytes. However, for the 1.1 kb region analyzed, no footprints were detected in a variety of cell types derived from patients with fragile X syndrome which have a transcriptionally inactive FMR1 gene. A BLAST nucleotide search identified sequence similarities between the region of the FMR1 gene containing the footprints and an analogous region within the promoter region of the gene for the heterogeneous nuclear ribonucleoprotein (hnRNP) A2, a member of a family of ribonucleoproteins implicated in mRNA processing and nuclear-cytoplasm transport. The nucleotide sequences identified in the hnRNP-A2 promoter region correspond to the same consensus binding sites showing DNA-protein interactions in the FMR1 gene. Our previous functional studies and the studies of others demonstrate that FMR proteins, like hnRNP-A2, are also ribonucleoproteins which appear to be involved in mRNA transport. The results from our footprint studies suggest that the expression of the FMR1 gene is regulated by the binding of specific transcription factors to sequence elements in the 5' region of the gene and that this expression may be regulated by elements in common with the hnRNP-A2 gene. Common regulation of these two genes might play an important role in the cooperative processing and transport of mRNA from the nucleus to the translation machinery.
Hum Mol Genet 1997 Nov
PMID:Structural and functional characterization of the human FMR1 promoter reveals similarities with the hnRNP-A2 promoter region. 932 68

In order to analyse the mechanism of cold shock induction of CspA, a major cold shock protein of Escherichia coli, deletion analysis of the cspA gene was carried out. It was found that (i) the AT-rich sequence (-47 to -38) upstream of the cspA -35 region may act as the UP element playing a crucial role in cspA transcription at both 37 degrees C and 15 degrees C; (ii) the unusually long 5'-UTR of the cspA mRNA has negative effects on cspA expression at 37 degrees C; and (iii) in contrast, the 5'-UTR exerts a positive effect on mRNA stabilization at low temperature. Furthermore, it was demonstrated that the 14 base downstream box (DB) locating 12 bases downstream of the initiation codon of the cspA mRNA and complementary to a region near the decoding region of 16S rRNA was essential for the mRNA translation during the growth lag acclimation phase immediately after cold shock. During this phase, translation of non-cold shock gene mRNAs is blocked, since they require cold shock-specific ribosomal factors for the formation of the translation initiation complex. It is proposed that DB in cold shock mRNAs allows the formation of a stable initiation complex at low temperature in the absence of the cold shock ribosomal factors.
Mol Microbiol 1997 Oct
PMID:Deletion analysis of cspA of Escherichia coli: requirement of the AT-rich UP element for cspA transcription and the downstream box in the coding region for its cold shock induction. 938 57

CR1 elements are a family of retroposons. They are classified as long interspersed elements (LINEs) or non-long-terminal-repeat (non-LTR) retrotransposons, and they have been found in the genomes of many vertebrates. However, they have been only partially characterized, and only a 2-kb region of the 3' end of chicken CR1 has been sequenced. In the present study, we determined the entire consensus sequence of CR1 elements in the turtle genome, designated PsCR1. The first open reading frame (ORF1) of PsCR1 has two unusual arrangements of Cys residues. One of them includes a zinc finger motif, CX2CX14CX2C. The putative zinc finger has cysteine residues with identical spacing and a similar amino acid composition to those found in the species-specific transcription initiation factors SL1 and TIF-IB. The 5' untranslated region (5' UTR) of PsCR1 contains a sequence similar to part of the human L1 promoter, L1 site A, and several cis elements of the type found in eukaryotic genes. Within a region of about 500 bp, there are nine "E boxes," cis elements that are recognized by the basic helix-loop-helix (bHLH) family of proteins. This observation raises the possibility that cellular transcription factors that bind to these sequences might act in concert to regulate the expression of PsCR1. The extent of the sequence divergence of the 3' UTR of CR1 between species was found to be lower than the rate of nonsynonymous substitutions per site in ORF2, suggesting that a strict functional constraint must exist for this region. This result strongly suggests that the conserved 3'-end sequence of CR1 is the recognition site for the reverse transcriptase of CR1. A discussion is presented of a possible mechanism for the integration of CR1 elements and also of the intriguing possible recruitment of the reverse transcriptase for the retroposition of SINEs.
Mol Biol Evol 1997 Dec
PMID:Determination of the entire sequence of turtle CR1: the first open reading frame of the turtle CR1 element encodes a protein with a novel zinc finger motif. 940 32

Autosomal dominant cerebellar ataxia with retinal degeneration (ADCAII) was previously mapped by linkage analysis studies to chromosome 3p12-p21.1 (SCA7). Positional cloning efforts have recently identified a novel gene, SCA7 , containing a translated CAG repeat, expanded in SCA7 patients. We cloned the SCA7 gene from a yeast artificial chromosome (YAC) clone contig spanning the SCA7 candidate region. Using a combination of genomic sequencing and cosmid-based exon trapping, two expressed sequence tags were identified. Sequencing of the corresponding cDNA clones and RT-PCR analysis identified the full-length SCA7 cDNA. Together, our sequence data defined the intron/exon boundaries of the first two coding exons of the SCA7 gene, with the first exon containing the expanded CAG repeat. Further, sequence comparison with the published SCA7 cDNA identified one additional putative exon in the 5'-UTR region of the SCA7 gene. The SCA7 gene was mapped on the YAC contig in the 2.5 cM interval between D3S1600 and D3S1287. In one extended Belgian SCA7 pedigree the expanded alleles ranged from 38 to at least 55 repeats with allele lengths being inversely correlated with onset age of ADCAII symptoms. The SCA7 repeats increased in length in successive generations. Normal alleles had from four to 18 repeats, with 10 repeats being the most common allele.
Hum Mol Genet 1998 Feb
PMID:Molecular genetic analysis of autosomal dominant cerebellar ataxia with retinal degeneration (ADCA type II) caused by CAG triplet repeat expansion. 942 24

The genetic basis of myotonic dystrophy (DM) is the expansion of an unstable CTG repeat in the 34 UTR of the DM protein kinase gene on chromosome 19. One of the principal features of the DM mutation is an extraordinarily high level of somatic mosaicism, due to an extremely high degree of somatic instability both within and between different tissues. This instability appears to be biased towards further expansion and continuous throughout the life of an individual, features that could be associated with the progressive nature of the disease. Although increasing measured allele size between patients clearly correlates with an increased severity of symptoms and an earlier age of onset, this correlation is not precise and measured allele length cannot be used as an accurate predictor of age of onset. In order to further characterize the dynamics of DM CTG repeat somatic instability, we have studied repeat length changes over time in 111 myotonic dystrophy patients with varying clinical severity and CTG repeat size over time intervals of 1-7 years. We have found a direct progression of the size heterogeneity over time related to initial CTG repeat size and the time interval and always biased towards further expansion. Attempts to mathematically model the dynamics have proved only partially successful suggesting that individual specific genetic and/or environmental factors also play a role in somatic mosaicism.
Hum Mol Genet 1998 Feb
PMID:Progression of somatic CTG repeat length heterogeneity in the blood cells of myotonic dystrophy patients. 942 39

The blood-brain barrier GLUT1 glucose transporter is under post-transcriptional regulation, and the 5'-untranslated region (5'-UTR) of the GLUT1 mRNA increases its translational rate in mammalian cells. To obtain more insight into the mechanism of translational control of GLUT1, the present investigation studied the translational efficiency of capped full-length synthetic human (h) and rabbit (rab) GLUT1 mRNA and both 5'- and 3'-UTR deleted hGLUT1 mRNAs in both mammalian and plant cell free translation systems. Translation efficiency of both h- and rabGLUT1 mRNA was increased 3- to 6-fold in rabbit retyculocyte lysate (RRL) compared with wheat germ extract (WGE). Confirming previous observations, deletion of 5'- and 5'/-3'-UTR markedly reduced the translation efficiency of the h-GLUT1 transcript in RRL. On the contrary, these deletions markedly increased the translation of GLUT1 in WGE. The present data provide additional evidence suggesting that the 5'-UTR of the GLUT1 mRNA contains cis-acting elements involved in the translational activation of the GLUT1 gene in mammalian cells and that factors involved in this cis/trans-acting interaction are either absent or down-regulated in plant systems.
Comp Biochem Physiol B Biochem Mol Biol 1997 Oct
PMID:The 5'-untranslated region of GLUT1 glucose transporter mRNA causes differential regulation of the translational rate in plant and animal systems. 944 Feb 23

The heat-stable antigen (HSA) is a costimulatory molecule for T-cell activation. Its expression is strictly regulated during lymphocyte development and differentiation. Recent studies using HSA-transgenic mice have demonstrated that this regulated expression is critical for normal development of T and B lymphocytes. However, the mechanisms that control the expression of HSA are largely unknown. HSA mRNA is comprised of a 0.23-kb open reading frame and a 1.5-kb 3' untranslated region (3'UTR). The function of the long 3'UTR has not been addressed. Here we investigate the role of the 3'UTR of HSA mRNA. We show that a 160-bp element, located in the region of nucleotides 1465 to 1625 in the 3'UTR of HSA mRNA, promotes RNA degradation and that this effect is neutralized by a 43-bp fragment approximately 1 kb upstream of the negative cis element. Both positive and negative cis elements in the HSA mRNA are distinct from other sequences that are known to modulate mRNA stability. These results provide direct evidence that the interplay between two novel cis elements in the 3'UTR of HSA mRNA determines cell surface HSA expression by modulating its RNA stability.
Mol Cell Biol 1998 Feb
PMID:Regulation of the stability of heat-stable antigen mRNA by interplay between two novel cis elements in the 3' untranslated region. 944 78

A general characteristic of the 3'-untranslated regions (3' UTRs) of plastid mRNAs is an inverted repeat (IR) sequence that can fold into a stem-loop structure. These stem-loops are RNA 3'-end processing signals and determinants of mRNA stability, not transcription terminators. Incubation of synthetic RNAs corresponding to the 3' UTRs of Chlamydomonas chloroplast genes atpB and petD with a chloroplast protein extract resulted in the accumulation of stable processing products. Synthetic RNAs of the petA 3' UTR and the antisense strand of atpB 3' UTR were degraded in the extract. To examine 3' UTR function in vivo, the atpB 3' UTR was replaced with the 3' UTR sequences of the Chlamydomonas chloroplast genes petD, petD plus trnR plus trnR, rbcL, petA and E. coli thrA by biolistic transformation of Chlamydomonas chloroplasts. Each 3' UTR was inserted in both the sense and antisense orientations. The accumulation of both total atpB mRNA and ATPase beta-subunit protein in all transformants was increased compared to a strain in which the atpB 3' UTR had been deleted. However, the level of discrete atpB transcripts in transformants containing the antisense 3' UTR sequences was reduced to approximately one-half that of transformants containing the 3' UTRs in the sense orientation. These results imply that both the nucleotide sequences and the stem-loop structures of the 3' UTRs are important for transcript 3'-end processing, and for accumulation of the mature mRNAs.
Plant Mol Biol 1998 Jan
PMID:The sequence and structure of the 3'-untranslated regions of chloroplast transcripts are important determinants of mRNA accumulation and stability. 948 42


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