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HuD Regulates Coding and Noncoding RNA to Induce APP→Aβ Processing

Kang, Min-Ju et al.

Cell reports. Volume 7:Number 5 (2014, June 12th); pp 1401-1409 -- Elsevier

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  • Title:
    HuD Regulates Coding and Noncoding RNA to Induce APP→Aβ Processing
  • Author: Kang, Min-Ju;
    Abdelmohsen, Kotb;
    Hutchison, Emmette R.;
    Mitchell, Sarah J.;
    Grammatikakis, Ioannis;
    Guo, Rong;
    Noh, Ji Heon;
    Martindale, Jennifer L.;
    Yang, Xiaoling;
    Lee, Eun Kyung;
    Faghihi, Mohammad A.;
    Wahlestedt, Claes;
    Troncoso, Juan C.;
    Pletnikova, Olga;
    Perrone-Bizzozero, Nora;
    Resnick, Susan M.;
    de Cabo, Rafael;
    Mattson, Mark P.;
    Gorospe, Myriam
  • Found In: Cell reports. Volume 7:Number 5 (2014, June 12th); pp 1401-1409
  • Journal Title: Cell reports
  • Subjects: Biology--Periodicals; Life sciences--Periodicals; Dewey: 571.6; Dewey: 571.6
  • Rights: Licensed
  • Publication Details: Elsevier
  • Abstract: Summary 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. Graphical Abstract Highlights RNA-binding protein HuD is elevated in Alzheimer's disease brain HuD binds to the APP and BACE1 3′ UTRs and increases APP and BACE1 levels HuD binds to and increases levels of long noncoding RNA BACE1AS HuD orchestrates APP synthesis and processing into Aβ Kang et al. now report that the neuronal RNA-binding protein HuD associates with three functionally related RNAs: amyloid precursor protein ( APP ) mRNA, encoding the Alzheimer's disease (AD)-related protein APP; BACE1 mRNA, encoding the APP-cleaving enzyme BACE1; and the long noncoding RNA BACE1AS, which binds to BACE1 mRNA and promotes BACE1 expression. Through these interactions, HuD enhances APP production and cleavage into the peptide Aβ. In keeping with these functions, HuD, APP, BACE1, and BACE1AS levels are elevated in AD brains.
  • Identifier: System Number: ETOCvdc_100062905632.0x000001; Journal ISSN: 2211-1247; 10.1016/j.celrep.2014.04.050
  • Publication Date: 2014
  • Physical Description: Electronic
  • UIN: ETOCvdc_100062905632.0x000001

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