Bergsdorf, C and Paliga, K and Kreger, S and Masters, CL and Beyreuther, K (2000) Identification of cis-elements regulating exon 15 splicing of the amyloid precursor protein pre-mRNA. JOURNAL OF BIOLOGICAL CHEMISTRY, 275 (3). pp. 2046-2056. ISSN 0021-9258,
Full text not available from this repository.Abstract
Alternative splicing of exon 15 of the amyloid precursor protein (APP) pre-mRNA generates two APP isoform groups App(ex15) (containing exon 15) and L-APP (without exon 15), which show a cell-specific distribution in non-neuronal cells and neurons of rat. Both APP isoforms differ in regard to functional properties like posttranslational modification, APP secretion, and proteolytic production of A beta peptide from APP molecules. Since A beta generation is an important factor in the development of Alzheimer's disease, one could anticipate that these major APP isoforms might contribute differentially to the mechanisms underlying neurodegeneration in Alzheimer's disease, In this study, we established an APP minigene system in a murine cell system to identify cis-acting elements controlling exon 15 recognition. A 12.5-kilobase pair genomic fragment of the murine APP gene contained all cis-regulatory elements to reproduce the splicing pattern of the endogenous APP transcripts. By using this approach, two intronic cis-elements flanking exon 15 were identified that block the inclusion of exon 15 in APP transcripts of non-neuronal cells. Point mutation analysis of these intronic regions indicated that pyrimidine-rich sequences are involved in the splice repressor function. Finally, grafting experiments demonstrated that these regulatory regions cell-specifically enhance the blockage of a chimeric exon in the non-neuronal splicing system.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CHONDROITIN SULFATE PROTEOGLYCANS; RNA SECONDARY STRUCTURE; MESSENGER-RNA; ALZHEIMERS-DISEASE; DEFAULT EXON; GENE; SELECTION; INTRON; EXPRESSION; CELLS; |
| Subjects: | 500 Science > 540 Chemistry & allied sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Biochemie, Genetik und Mikrobiologie > Lehrstuhl für Biochemie I > Prof. Dr. Gunter Meister |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 20 May 2021 06:23 |
| Last Modified: | 20 May 2021 06:23 |
| URI: | https://pred.uni-regensburg.de/id/eprint/42887 |
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