2. Academic Validation
  3. HuD regulates coding and noncoding RNA to induce APP→Aβ processing

HuD regulates coding and noncoding RNA to induce APP→Aβ processing

  • Cell Rep. 2014 Jun 12;7(5):1401-1409. doi: 10.1016/j.celrep.2014.04.050.
Min-Ju Kang 1,  Kotb Abdelmohsen 1,  Emmette R Hutchison 2,  Sarah J Mitchell 3,  Ioannis Grammatikakis 1,  Rong Guo 1,  Ji Heon Noh 1,  Jennifer L Martindale 1,  Xiaoling Yang 1,  Eun Kyung Lee 1,  Mohammad A Faghihi 4,  Claes Wahlestedt 4,  Juan C Troncoso 5,  Olga Pletnikova 5,  Nora Perrone-Bizzozero 6,  Susan M Resnick 7,  Rafael de Cabo 3,  Mark P Mattson 2,  Myriam Gorospe 8
Affiliations

Affiliations

  • 1 Laboratory of Genetics, National Institute on Aging-Intramural Research Program, NIH, Baltimore, MD 21224, USA.
  • 2 Laboratory of Neurosciences, National Institute on Aging-Intramural Research Program, NIH, Baltimore, MD 21224, USA.
  • 3 Translational Gerontology Branch, National Institute on Aging-Intramural Research Program, NIH, Baltimore, MD 21224, USA.
  • 4 Center for Therapeutic Innovation, University of Miami, Miller School of Medicine, Miami, FL 33136, USA.
  • 5 Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  • 6 Department of Neurosciences, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA.
  • 7 Laboratory of Behavioral Neuroscience, National Institute on Aging-Intramural Research Program, NIH, Baltimore, MD 21224, USA.
  • 8 Laboratory of Genetics, National Institute on Aging-Intramural Research Program, NIH, Baltimore, MD 21224, USA. Electronic address: [email protected].
PMID: 24857657 DOI: 10.1016/j.celrep.2014.04.050
Abstract

The primarily neuronal RNA-binding protein HuD is implicated in learning and memory. Here, we report the identification of several HuD target transcripts linked to Alzheimer's disease (AD) pathogenesis. HuD interacted with the 3' UTRs of APP mRNA (encoding amyloid precursor protein) and BACE1 mRNA (encoding β-site APP-cleaving Enzyme 1) and increased the half-lives of these mRNAs. HuD also associated with and stabilized the long noncoding (lnc)RNA BACE1AS, which partly complements BACE1 mRNA and enhances BACE1 expression. Consistent with HuD promoting production of APP and APP-cleaving Enzyme, the levels of APP, BACE1, BACE1AS, and Aβ were higher in the brain of HuD-overexpressing mice. Importantly, cortex (superior temporal gyrus) from patients with AD displayed significantly higher levels of HuD and, accordingly, elevated APP, BACE1, BACE1AS, and Aβ than did cortical tissue from healthy age-matched individuals. We propose that HuD jointly promotes the production of APP and the cleavage of its amyloidogenic fragment, Aβ.

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