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

被引：91

作者：

Kang, Min-Ju ^{[1
]}

Abdelmohsen, Kotb ^{[1
]}

Hutchison, Emmette R. ^{[2
]}

Mitchell, Sarah J. ^{[3
]}

Grammatikakis, Ioannis ^{[1
]}

Guo, Rong ^{[1
]}

Noh, Ji Heon ^{[1
]}

Martindale, Jennifer L. ^{[1
]}

Yang, Xiaoling ^{[1
]}

Lee, Eun Kyung ^{[1
]}

Faghihi, Mohammad A. ^{[5
]}

Wahlestedt, Claes ^{[5
]}

Troncoso, Juan C. ^{[6
]}

Pletnikova, Olga ^{[6
]}

Perrone-Bizzozero, Nora ^{[7
]}

Resnick, Susan M. ^{[4
]}

De Cabo, Rafael ^{[3
]}

Mattson, Mark P. ^{[2
]}

Gorospe, Myriam ^{[1
]}

机构：

[1] Natl Inst Aging Intramural Res Program, Genet Lab, NIH, Baltimore, MD 21224 USA

[2] Natl Inst Aging Intramural Res Program, Lab Neurosci, NIH, Baltimore, MD 21224 USA

[3] Natl Inst Aging Intramural Res Program, Translat Gerontol Branch, NIH, Baltimore, MD 21224 USA

[4] Natl Inst Aging Intramural Res Program, Lab Behav Neurosci, NIH, Baltimore, MD 21224 USA

[5] Univ Miami, Miller Sch Med, Ctr Therapeut Innovat, Miami, FL 33136 USA

[6] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA

[7] Univ New Mexico, Sch Med, Dept Neurosci, Albuquerque, NM 87131 USA

来源：

CELL REPORTS | 2014年 / 7卷 / 05期

关键词：

BINDING PROTEIN HUD; POSTTRANSCRIPTIONAL GENE-REGULATION; NEURONAL DIFFERENTIATION; TRANSLATION; EXPRESSION; CELLS;

D O I：

10.1016/j.celrep.2014.04.050

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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 beta-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 A beta 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 A beta 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, A beta.

引用

页码：1401 / 1409

页数：9

共 23 条

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