Decoy mRNAs reduce β-amyloid precursor protein mRNA in neuronal cells

Pamela R. Westmark, Hyun C. Shin, Cara J. Westmark, Syrus R. Soltaninassab, Emily K. Reinke, James S. Malter

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Overproduction of amyloid precursor protein (APP) and β-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.

Original languageEnglish (US)
Pages (from-to)787-796
Number of pages10
JournalNeurobiology of Aging
Volume27
Issue number6
DOIs
StatePublished - Jun 1 2006

Keywords

  • 3′-UTR regulatory elements
  • Alzheimer's disease
  • mRNA stability
  • β-Amyloid precursor protein

ASJC Scopus subject areas

  • Neuroscience(all)
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

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