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The human brain has distinct regional expression patterns of estrogen receptor alpha mRNA isoforms derived from alternative promoters 总被引:1,自引:0,他引:1
The human estrogen receptor (ER) alpha gene is transcribed from multiple promoters, generating mRNA isoforms with unique 5' ends in the untranslated region. In the present study, alternative promoters were shown to regulate the ERalpha gene expression in different neuronal populations of the human brain. By using in situ hybridization histochemistry, the A and B promoters, but not the C promoter, in the ERalpha gene were found to be active in the human forebrain. The mRNA isoform transcribed from the A promoter was expressed in low levels in most of the brain areas where ERalpha mRNA was present. In contrast, the B promoter mRNA isoform was more restricted, localized predominantly in high-expressing ERalpha mRNA regions. The gross anatomical distribution of the different mRNA isoforms analyzed with RT-PCR generally supported the results obtained by the in situ hybridization. Estrogen is known to modulate many different brain functions, such as neuroendocrine events associated with reproduction, mood, and cognition, likely to be mediated by different neuronal populations. Thus, the current findings of alternative ERalpha promoter expression in distinct neuronal populations suggest that multiple promoter usage is a possible mechanism to achieve differentiated regulation of the ERalpha expression, dependent on the cell phenotype and consequently the functions mediated by the specific neuron. 相似文献
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CTP:phosphoethanolamine cytidylyltransferase (Pcyt2) has an important regulatory function in biosynthesis of the membrane phospholipid phosphatidylethanolamine. We previously determined that the full-length Pcyt2α and its splice variant Pcyt2β are the main active isoforms of this enzyme. Here we report that mouse Pcyt2 could be spliced at Introns 7 and 8 to produce a unique third isoform, Pcyt2γ, in which the second cytidylyltransferase domain at the C-terminus becomes deleted. Pcyt2γ is ubiquitously expressed in embryonic and adult mouse tissues, and is the most abundant in the kidney, skeletal muscle and testis. Pcyt2γ splicing mechanism dominates over Pcyt2β exon-skipping mechanism in most examined tissues. Although Pcyt2γ maintains the N-terminal cytidylyltransferase domain as most cytidylyltransferases, the lack of the C-terminal cytidylyltransferase domain causes a complete loss of catalytic activity. However, Pcyt2γ interacts with the active isoform, Pcyt2α, and significantly reduces Pcyt2α homodimerization and activity. The inactive N-domain (H35Y, H35A) and C-domain (H244Y, H244A) mutants of Pcyt2α also reduce Pcyt2α homodimerization and activity. This study revealed the importance of both cytidylyltransferase 35HYGH and 244HIGH motifs for the activity of murine Pcyt2α and established that the naturally occurring splice variant Pcyt2γ has a function to restrain the enzyme activity through the formation of unproductive enzyme complexes. 相似文献
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Four fibroblast tropomyosin isoforms are expressed from the rat alpha-tropomyosin gene via alternative RNA splicing and the use of two promoters 总被引:11,自引:0,他引:11
L O Goodwin J P Lees-Miller M A Leonard S B Cheley D M Helfman 《The Journal of biological chemistry》1991,266(13):8408-8415
cDNA clones encoding four rat tropomyosin isoforms, termed TM-2, TM-3, TM-5a, and TM-5b, were isolated and characterized. All are derived from the alpha-tropomyosin gene via alternative RNA processing and the use of two alternate promoters. The cDNA sequences predict that TM-2 and TM-3 both contain 284 amino acids and differ from each other only at an internal region of the protein from amino acids 189 through 213, due to alternative splicing of exons 6a and 6b. TM-5a and TM-5b both contain 248 amino acids and differ from each other only at an internal exon encoding amino acids 153 through 177, also due to alternative splicing of exons 6a and 6b. The differences in the amino acid sequence encoded by these alternate exons affects the theoretical actin-binding pattern of the tropomyosins, such that TM-5b is expected to bind actin with greater affinity than TM-5a. TM-2 and TM-3 are transcribed from the upstream promoter, and TM-5a and TM-5b are transcribed from an internal promoter. In addition, all four isoforms contain the identical COOH-terminal coding region. RNA protection analyses revealed that the mRNA for each isoform is expressed in a number of different tissues and cell types, although the expression of some isoforms is restricted to particular cell types. Furthermore, the expression of mRNA encoding these isoforms was found to be altered in a number of different virally transformed cell lines. The changes in the expression of tropomyosin mRNAs in transformed cells reflect changes in the relative use of the two promoters, as well as the relative use of alternatively spliced exons 6a and 6b. 相似文献
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CTP:phosphocholine cytidylyltransferase is a major regulator of phosphatidylcholine biosynthesis. A single isoform, CCTalpha, has been studied extensively and a second isoform, CCTbeta, was recently identified. We identify and characterize a third cDNA, CCTbeta2, that differs from CCTbeta1 at the carboxyl-terminal end and is predicted to arise as a splice variant of the CCTbeta gene. Like CCTalpha, CCTbeta2 is heavily phosphorylated in vivo, in contrast to CCTbeta1. CCTbeta1 and CCTbeta2 mRNAs were differentially expressed by the human tissues examined, whereas CCTalpha was more uniformly represented. Using isoform-specific antibodies, both CCTbeta1 and CCTbeta2 localized to the endoplasmic reticulum of cells, in contrast to CCTalpha which resided in the nucleus in addition to associating with the endoplasmic reticulum. CCTbeta2 protein has enzymatic activity in vitro and was able to complement the temperature-sensitive cytidylyltransferase defect in CHO58 cells, just as CCTalpha and CCTbeta1 supporting proliferation at the nonpermissive conditions. Overexpression experiments did not reveal discrete physiological functions for the three isoforms that catalyze the same biochemical reaction; however, the differential cellular localization and tissue-specific distribution suggest that CCTbeta1 and CCTbeta2 may play a role that is distinct from ubiquitously expressed CCTalpha. 相似文献
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Ziak M Meier M Etter KS Roth J 《Biochemical and biophysical research communications》2001,280(1):363-367
We previously cloned glucosidase II and provided in vivo evidence for its involvement in protein folding quality control. DNA-sequencing of different clones demonstrated the existence of two isoforms of glucosidase II which differed by 66 nucleotides due to alternative splicing. The existence of two enzyme isoforms in various organs of pig and rat as well as human, bovine, rat, and mouse cell lines could be demonstrated by RT-PCR and Western blotting. Furthermore, the two isoforms of glucosidase II could be detected in embryonic and postnatal rat kidney and liver. In yeast, Saccharomyces cerevisiae, and in insects, Drosophila S2 cells, only one isoforms of the enzyme was detectable. The ubiquitous occurrence of the two glucosidase II isoforms in mammalian tissues and cell lines might be indicative of a special function of each isoform. 相似文献
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TIA-1 (T-cell Intracellular Antigen 1) and TIAR (TIA-1-related protein) are RNA-binding proteins involved in the regulation of alternative pre-mRNA splicing and other aspects of RNA metabolism. Various isoforms of these proteins exist in mammals. For example, TIA-1 presents two major isoforms (TIA-1a and TIA-1b) generated by alternative splicing of exon 5 that differ by eleven amino acids exclusive of the TIA-1a isoform. Here we show that the relative expression of TIA-1 and TIAR isoforms varies in different human tissues and cell lines, suggesting distinct functional properties and regulated isoform expression. We report that whereas TIA-1 isoforms show similar subcellular distribution and RNA binding, TIA-1b displays enhanced splicing stimulatory activity compared with TIA-1a, both in vitro and in vivo. Interestingly, TIAR depletion from HeLa and mouse embryonic fibroblasts results in an increased ratio of TIA-1b/a expression, suggesting that TIAR regulates the relative expression of TIA-1 isoforms. Taken together, the results reveal distinct functional properties of TIA-1 isoforms and the existence of a regulatory network that controls isoform expression. 相似文献