Abstract |
Overproduction of amyloid precursor protein (APP) and beta-amyloid likely contribute to neurodegeneration in Alzheimer's disease (AD). In an effort to understand neuronal APP gene regulation, we identified a 52 base element (52sce) immediately downstream from the stop codon that stabilizes APP mRNA. Deletion of this domain drastically destabilized APP mRNAs and reduced APP synthesis in vitro. Chimeric globin-APP mRNAs containing the globin coding sequence fused to the entire APP 3'-UTR, showed regulation similar to full-length APP mRNA. A variety of cytoplasmic lysates contain 52sce RNA binding activity, suggesting cis-trans interactions regulate the element's functionality. Finally, the overexpression of chimeric mRNAs, containing the GFP coding sequence and APP 3'-UTR, dramatically reduced endogenous APP steady-state levels in SH-SY5Y neuroblastoma cells and suggests a novel approach to reduce the amyloid burden in AD patients.
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Authors | Pamela R Westmark, Hyun C Shin, Cara J Westmark, Syrus R Soltaninassab, Emily K Reinke, James S Malter |
Journal | Neurobiology of aging
(Neurobiol Aging)
Vol. 27
Issue 6
Pg. 787-96
(Jun 2006)
ISSN: 0197-4580 [Print] United States |
PMID | 16672170
(Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- 3' Untranslated Regions
- Amyloid beta-Protein Precursor
- RNA, Messenger
- Green Fluorescent Proteins
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Topics |
- 3' Untranslated Regions
(physiology)
- Amyloid beta-Protein Precursor
(genetics, metabolism)
- Base Sequence
- Blotting, Northern
(methods)
- Cell Line
- Electrophoretic Mobility Shift Assay
(methods)
- Gene Expression Regulation
(physiology)
- Green Fluorescent Proteins
(biosynthesis)
- Humans
- Models, Molecular
- Mutagenesis
(physiology)
- Neurons
(physiology)
- Protein Biosynthesis
- RNA, Messenger
(metabolism)
- Reverse Transcriptase Polymerase Chain Reaction
(methods)
- Time Factors
- Transcription, Genetic
- Transfection
(methods)
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