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

Published

Journal Article

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.

Full Text

Cited Authors

  • Westmark, PR; Shin, HC; Westmark, CJ; Soltaninassab, SR; Reinke, EK; Malter, JS

Published Date

  • June 2006

Published In

Volume / Issue

  • 27 / 6

Start / End Page

  • 787 - 796

PubMed ID

  • 16672170

Pubmed Central ID

  • 16672170

Electronic International Standard Serial Number (EISSN)

  • 1558-1497

International Standard Serial Number (ISSN)

  • 0197-4580

Digital Object Identifier (DOI)

  • 10.1016/j.neurobiolaging.2006.03.003

Language

  • eng