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

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

doi:10.1016/j.celrep.2014.04.050

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

Journal article

Open access

Peer reviewed

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

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, …

Cell reports (Cambridge), Vol.7(5), pp.1401-1409

2014-06-12

DOI: https://doi.org/10.1016/j.celrep.2014.04.050

PMCID: PMC4074355

PMID: 24857657

Abstract

Amyloid Precursor Protein Secretases - genetics

Humans

Mice, Inbred C57BL

Middle Aged

ELAV Proteins - metabolism

Male

RNA, Long Noncoding - genetics

Aspartic Acid Endopeptidases - genetics

RNA Stability

Case-Control Studies

Cerebral Cortex - metabolism

Amyloid Precursor Protein Secretases - metabolism

Animals

Aspartic Acid Endopeptidases - metabolism

Alzheimer Disease - metabolism

Amyloid beta-Peptides - metabolism

Aged, 80 and over

Cell Line, Tumor

Female

Aged

Mice

3' Untranslated Regions

ELAV Proteins - genetics

RNA, Long Noncoding - metabolism

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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Collaboration types: Domestic collaboration
Citation topics: 1 Clinical & Life Sciences; 1.54 Molecular & Cell Biology - Genetics; 1.54.469 Splicing
Web Of Science research areas: Cell Biology
ESI research areas: Molecular Biology & Genetics

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Title: HuD regulates coding and noncoding RNA to induce APP→Aβ processing
Creators: Min-Ju Kang - Laboratory of Genetics, National Institute on Aging-Intramural Research Program, NIH, Baltimore, MD 21224, USA
Kotb Abdelmohsen - Laboratory of Genetics, National Institute on Aging-Intramural Research Program, NIH, Baltimore, MD 21224, USA
Emmette R Hutchison - Laboratory of Neurosciences, National Institute on Aging-Intramural Research Program, NIH, Baltimore, MD 21224, USA
Sarah J Mitchell - Translational Gerontology Branch, National Institute on Aging-Intramural Research Program, NIH, Baltimore, MD 21224, USA
Ioannis Grammatikakis - Laboratory of Genetics, National Institute on Aging-Intramural Research Program, NIH, Baltimore, MD 21224, USA
Rong Guo - Laboratory of Genetics, National Institute on Aging-Intramural Research Program, NIH, Baltimore, MD 21224, USA
Ji Heon Noh - Laboratory of Genetics, National Institute on Aging-Intramural Research Program, NIH, Baltimore, MD 21224, USA
Jennifer L Martindale - Laboratory of Genetics, National Institute on Aging-Intramural Research Program, NIH, Baltimore, MD 21224, USA
Xiaoling Yang - Laboratory of Genetics, National Institute on Aging-Intramural Research Program, NIH, Baltimore, MD 21224, USA
Eun Kyung Lee - Laboratory of Genetics, National Institute on Aging-Intramural Research Program, NIH, Baltimore, MD 21224, USA
Mohammad A Faghihi - Center for Therapeutic Innovation, University of Miami, Miller School of Medicine, Miami, FL 33136, USA
Claes Wahlestedt - Center for Therapeutic Innovation, University of Miami, Miller School of Medicine, Miami, FL 33136, USA
Juan C Troncoso - Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Olga Pletnikova - Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Nora Perrone-Bizzozero - Department of Neurosciences, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA
Susan M Resnick - Laboratory of Behavioral Neuroscience, National Institute on Aging-Intramural Research Program, NIH, Baltimore, MD 21224, USA
Rafael de Cabo - Translational Gerontology Branch, National Institute on Aging-Intramural Research Program, NIH, Baltimore, MD 21224, USA
Mark P Mattson - Laboratory of Neurosciences, National Institute on Aging-Intramural Research Program, NIH, Baltimore, MD 21224, USA
Myriam Gorospe - Laboratory of Genetics, National Institute on Aging-Intramural Research Program, NIH, Baltimore, MD 21224, USA. Electronic address: myriam-gorospe@nih.gov
Publication Details: Cell reports (Cambridge), Vol.7(5), pp.1401-1409
Publisher: United States
Grant note: P50AG05146 / NIA NIH HHS ZIA AG000518-09 / Intramural NIH HHS R01DA034097 / NIDA NIH HHS R01 DA034097 / NIDA NIH HHS P50 AG005146 / NIA NIH HHS
Academic Unit: Miller School of Medicine; UMMG Dept of Psychiatry & Behavioral Sciences
Language: English
Resource Type: Journal article
PMID: 24857657
PMCID: PMC4074355
Record Identifier: 991031576805802976