Decoy mRNAs reduce beta-amyloid precursor protein mRNA in neuronal cells
| Autor: | Hyun Cheol Shin, Emily K. Reinke, Cara J. Westmark, Pamela R. Westmark, James S. Malter, Syrus R. Soltaninassab |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Untranslated region
Models Molecular Aging Time Factors Transcription Genetic Green Fluorescent Proteins Electrophoretic Mobility Shift Assay Biology Transfection Cell Line Amyloid beta-Protein Precursor mental disorders Protein biosynthesis Amyloid precursor protein Coding region Humans RNA Messenger 3' Untranslated Regions Regulation of gene expression Neurons Messenger RNA Base Sequence Three prime untranslated region Reverse Transcriptase Polymerase Chain Reaction General Neuroscience P3 peptide Blotting Northern Molecular biology Gene Expression Regulation Mutagenesis Protein Biosynthesis biology.protein Neurology (clinical) Geriatrics and Gerontology Developmental Biology |
| Zdroj: | Neurobiology of aging. 27(6) |
| ISSN: | 0197-4580 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect