Amyloid precursor protein, an androgen-regulated gene, is targeted by RNA-binding protein PSF/SFPQ in neuronal cells.
Alzheimer Disease
/ genetics
Amyloid beta-Protein Precursor
/ genetics
Androgens
/ genetics
Animals
Brain
/ metabolism
Cell Line
Disease Models, Animal
Gene Knockdown Techniques
Humans
Mice
Neurons
/ metabolism
PTB-Associated Splicing Factor
/ genetics
Protein Binding
RNA, Messenger
/ metabolism
RNA-Binding Proteins
/ metabolism
Receptors, Androgen
Transcriptome
Up-Regulation
RNA-binding protein
amyloid precursor protein
androgen receptor
neuron
protein-associated splicing factor
splicing
transcription
Journal
Genes to cells : devoted to molecular & cellular mechanisms
ISSN: 1365-2443
Titre abrégé: Genes Cells
Pays: England
ID NLM: 9607379
Informations de publication
Date de publication:
Nov 2019
Nov 2019
Historique:
received:
14
06
2019
revised:
09
09
2019
accepted:
14
09
2019
pubmed:
22
9
2019
medline:
17
3
2020
entrez:
22
9
2019
Statut:
ppublish
Résumé
Amyloid precursor protein (APP) is a representative gene related to Alzheimer's disease (AD). Androgens function by binding to the androgen receptor (AR). Both androgen and RNA-binding protein PSF play a role in the pathology of AD. However, the involvement of AR and PSF in APP regulation in neuron has not been investigated. Here, we explored the regulatory mechanism of APP expression by AR and PSF using neuron-derived cells. We demonstrated that androgen up-regulates the production of APP at the mRNA and protein levels. This induction is enhanced by AR over-expression and inhibited by its silencing. One candidate AR-binding region was identified in the intron region of APP and validated its activity as AR-dependent enhancer by the luciferase assay. Furthermore, the public transcriptome data of brain tissues of mice indicated that APP is regulated by PSF post-transcriptionally. We observed a decreased expression of APP after PSF knockdown and interaction of PSF with the APP transcript. Moreover, we revealed that silencing of PSF inhibited the stability of the APP mRNA. Thus, these results presented a new regulatory mechanism of APP expression by androgen through AR-mediated transcription and PSF at the post-transcriptional level that might be associated with the occurrence of AD.
Substances chimiques
Amyloid beta-Protein Precursor
0
Androgens
0
PTB-Associated Splicing Factor
0
RNA, Messenger
0
RNA-Binding Proteins
0
Receptors, Androgen
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
719-730Subventions
Organisme : Takeda Science Foundation
Organisme : Japan Society for the Promotion of Science
ID : 17H04334
Organisme : P-CREATE
ID : JP18cm0106144
Informations de copyright
© 2019 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.
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