title: 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.
authors: Department of Pathology and Laboratory Medicine, Neuroscience Training Program, Waisman Center for Developmental Disabilities and Institute on Aging, University of Wisconsin-Madison, 1500 Highland Avenue, Madison, WI 53705, USA.
authors: Pamela R
authors: PR
authors: Westmark
authors: Hyun C
authors: HC
authors: Shin
authors: Cara J
authors: CJ
authors: Westmark
authors: Syrus R
authors: SR
authors: Soltaninassab
authors: Emily K
authors: EK
authors: Reinke
authors: James S
authors: JS
authors: Malter