| Literature DB >> 24857657 |
Min-Ju Kang1, Kotb Abdelmohsen1, Emmette R Hutchison2, Sarah J Mitchell3, Ioannis Grammatikakis1, Rong Guo1, Ji Heon Noh1, Jennifer L Martindale1, Xiaoling Yang1, Eun Kyung Lee1, Mohammad A Faghihi4, Claes Wahlestedt4, Juan C Troncoso5, Olga Pletnikova5, Nora Perrone-Bizzozero6, Susan M Resnick7, Rafael de Cabo3, Mark P Mattson2, Myriam Gorospe8.
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.Entities:
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Year: 2014 PMID： 24857657 PMCID： PMC4074355 DOI： 10.1016/j.celrep.2014.04.050
Source DB: PubMed Journal: Cell Rep Impact factor: 9.423