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- Title
Expression of a noncoding RNA is elevated in Alzheimer's disease and drives rapid feed-forward regulation of beta-secretase.
- Authors
Faghihi, Mohammad Ali; Modarresi, Farzaneh; Khalil, Ahmad M; Wood, Douglas E; Sahagan, Barbara G; Morgan, Todd E; Finch, Caleb E; St Laurent, Georges, 3rd; Kenny, Paul J; Wahlestedt, Claes
- Abstract
Recent efforts have revealed that numerous protein-coding messenger RNAs have natural antisense transcript partners, most of which seem to be noncoding RNAs. Here we identify a conserved noncoding antisense transcript for beta-secretase-1 (BACE1), a crucial enzyme in Alzheimer's disease pathophysiology. The BACE1-antisense transcript (BACE1-AS) regulates BACE1 mRNA and subsequently BACE1 protein expression in vitro and in vivo. Upon exposure to various cell stressors including amyloid-beta 1-42 (Abeta 1-42), expression of BACE1-AS becomes elevated, increasing BACE1 mRNA stability and generating additional Abeta 1-42 through a post-transcriptional feed-forward mechanism. BACE1-AS concentrations were elevated in subjects with Alzheimer's disease and in amyloid precursor protein transgenic mice. These data show that BACE1 mRNA expression is under the control of a regulatory noncoding RNA that may drive Alzheimer's disease-associated pathophysiology. In summary, we report that a long noncoding RNA is directly implicated in the increased abundance of Abeta 1-42 in Alzheimer's disease.
- Publication
Nature medicine, 2008, Vol 14, Issue 7, p723
- ISSN
1546-170X
- Publication type
Journal Article
- DOI
10.1038/nm1784