作者
Min-Ju Kang, Kotb Abdelmohsen, Emmette R Hutchison, Sarah J Mitchell, Ioannis Grammatikakis, Rong Guo, Ji Heon Noh, Jennifer L Martindale, Xiaoling Yang, Eun Kyung Lee, Mohammad A Faghihi, Claes Wahlestedt, Juan C Troncoso, Olga Pletnikova, Nora Perrone-Bizzozero, Susan M Resnick, Rafael De Cabo, Mark P Mattson, Myriam Gorospe
发表日期
2014/6/12
期刊
Cell reports
卷号
7
期号
5
页码范围
1401-1409
出版商
Cell Press
简介
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 …
引用总数
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