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Decoy mRNAs reduce beta-amyloid precursor protein mRNA in neuronal cells.

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.
AuthorsPamela R Westmark, Hyun C Shin, Cara J Westmark, Syrus R Soltaninassab, Emily K Reinke, James S Malter
JournalNeurobiology of aging (Neurobiol Aging) Vol. 27 Issue 6 Pg. 787-96 (Jun 2006) ISSN: 0197-4580 [Print] United States
PMID16672170 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural)
Chemical References
  • 3' Untranslated Regions
  • Amyloid beta-Protein Precursor
  • RNA, Messenger
  • Green Fluorescent Proteins
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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