Amyloid precursor protein, an androgen‐regulated gene, is targeted by RNA‐binding protein PSF/SFPQ in neuronal cells. (15th October 2019)

• Record Type: Journal Article
• Authors: Takayama, Ken‐ichi; Fujiwara, Kyoko; Inoue, Satoshi
• Is Part Of: Genes to cells. Volume 24:Number 11(2019)
• Page Start: 719
• Page End: 730
• Publication Date: 2019-10-15
• Subjects: amyloid precursor protein -- androgen receptor -- neuron -- protein‐associated splicing factor -- RNA‐binding protein -- splicing -- transcription; Cytogenetics -- Periodicals; Cells -- Mechanical properties -- Periodicals; Molecular genetics -- Periodicals; Genes -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Biomechanics -- Periodicals; 571.6
• DOI: 10.1111/gtc.12721
• Languages: English
• ISSNs: 1356-9597

Abstract

Abstract: 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. Abstract : Amyloid precursor protein (APP) is a representative gene related to Alzheimer's disease (AD). In this study, we report that APP is directly regulated by androgen receptor and PSF, RNA binding protein associated with AD, in neuronal cells. Our findings shed light on the new role of RNA binding proteins in regulating APP in neuron.