Exon

About: Exon is a research topic. Over the lifetime, 38308 publications have been published within this topic receiving 1745408 citations. The topic is also known as: exons.

Peroxisome Proliferator Activated Receptor-α Expression in Human Liver

Abstract: The peroxisome proliferator activated receptor alpha (PPAR) is a member of the steroid/hormone receptor superfamily that mediates the peroxisome proliferator-dependent transcriptional activation of genes encoding several peroxisomal and microsomal enzymes as well as peroxisome proliferation. Human liver is refractory to the pathological effects of peroxisome proliferators that are seen in mice. With the use of RNase protection assays, the ratio of hepatic PPAR alpha mRNA to beta-actin mRNA was found to be 1 order of magnitude lower in humans than that observed in mice. In addition, the isolation of human cDNA for PPAR alpha that does not encode a functional PPAR because it lacks exon 6 as a result of alternate RNA splicing suggested that this process might also diminish the expression of PPAR alpha. RNase protection analysis of total RNA revealed the presence of splice variants lacking exon 6 at significant levels in all 10 human liver samples examined. Supershift analysis using the CYP4A6-Z peroxisome proliferator response element and antisera specific for PPAR alpha revealed easily detectable amounts of PPAR alpha DNA binding activity in mouse liver lysates, whereas human liver lysates contained > 10-fold lower amounts of PPAR alpha DNA binding activity. In contrast to mouse lysates, the amount of PPAR alpha binding in human lysates was generally less than that of other unidentified proteins. These results suggest that although humans retain the coding potential for a functional receptor, the low levels of PPAR alpha expression in liver may be insufficient to compete effectively with other proteins that bind to peroxisome proliferator response elements.

Cloning of the cDNA and gene for a human D2 dopamine receptor.

Abstract: A clone encoding a human D2 dopamine receptor was isolated from a pituitary cDNA library and sequenced. The deduced protein sequence is 96% identical with that of the cloned rat receptor with one major difference: the human receptor contains an additional 29 amino acids in its putative third cytoplasmic loop. Southern blotting demonstrated the presence of only one human D2 receptor gene. Two overlapping phage containing the gene were isolated and characterized. DNA sequence analysis of these clones showed that the coding sequence is interrupted by six introns and that the additional amino acids present in the human pituitary receptor are encoded by a single exon of 87 base pairs. The involvement of this sequence in alternative splicing and its biological significance are discussed.

EWS-FLI1 fusion transcript structure is an independent determinant of prognosis in Ewing's sarcoma.

Abstract: PURPOSEMore than 90% of Ewing's sarcomas (ES) contain a fusion of the EWS and FLI1 genes, due to the t(11;22)(q24;q12) translocation. At the molecular level, the EWS-FLI1 rearrangements show great diversity. Specifically, many different combinations of exons from EWS and FLI1 encode in-frame fusion transcripts and result in differences in the length and composition of the chimeric protein, which functions as an oncogenic aberrant transcription factor. In the most common fusion type (type 1), EWS exon 7 is linked in frame with exon 6 of FLI1. As the fundamental pathogenetic lesion in ES, the molecular heterogeneity of these fusion transcripts may have functional and clinical significance.PATIENTS AND METHODSWe performed a clinical and pathologic analysis of 112 patients with ES in which EWS-FLI1 fusion transcripts were identified by reverse-transcriptase polymerase chain reaction (RT-PCR). Adequate treatment and follow-up data were available in 99 patients treated with curative intent. Median follow-up in ...

Pathogenic implications of mutations in the tau gene in pallido-ponto-nigral degeneration and related neurodegenerative disorders linked to chromosome 17

Abstract: Pallido-ponto-nigral degeneration (PPND) is one of the most well characterized familial neurodegenerative disorders linked to chromosome 17q21-22. These hereditary disorders are known collectively as frontotemporal dementia (FTD) and parkinsonism linked to chromosome 17 (FTDP-17). Although the clinical features and associated regional variations in the neuronal loss observed in different FTDP-17 kindreds are diverse, the diagnostic lesions of FTDP-17 brains are tau-rich filaments in the cytoplasm of specific subpopulations of neurons and glial cells. The microtubule associated protein (tau) gene is located on chromosome 17q21-22. For these reasons, we investigated the possibility that PPND and other FTDP-17 syndromes might be caused by mutations in the tau gene. Two missense mutations in exon 10 of the tau gene that segregate with disease, Asn279(Lys) in the PPND kindred and Pro301(Leu) in four other FTDP-17 kindreds, were found. A third mutation was found in the intron adjacent to the 3' splice site of exon 10 in patients from another FTDP-17 family. Transcripts that contain exon 10 encode tau isoforms with four microtubule (MT)-binding repeats (4Rtau) as opposed to tau isoforms with three MT-binding repeats (3Rtau). The insoluble tau aggregates isolated from brains of patients with each mutation were analyzed by immunoblotting using tau-specific antibodies. For each of three mutations, abnormal tau with an apparent Mr of 64 and 69 was observed. The dephosphorylated material comigrated with tau isoforms containing exon 10 having four MT-binding repeats but not with 3Rtau. Thus, the brains of patients with both the missense mutations and the splice junction mutation contain aggregates of insoluble 4Rtau in filamentous inclusions, which may lead to neurodegeneration.