17ß-estradiol regulates the RNA-binding protein Nova1, which then regulates the alternative splicing of estrogen receptor ß in the aging female rat brain.
Neurobiol Aging
; 61: 13-22, 2018 01.
Article
in En
| MEDLINE
| ID: mdl-29031089
ABSTRACT
Alternative RNA splicing results in the translation of diverse protein products arising from a common nucleotide sequence. These alternative protein products are often functional and can have widely divergent actions from the canonical protein. Studies in humans and other vertebrate animals have demonstrated that alternative splicing events increase with advanced age, sometimes resulting in pathological consequences. Menopause represents a critical transition for women, where the beneficial effects of estrogens are no longer evident; therefore, factors underlying increased pathological conditions in women are confounded by the dual factors of aging and declining estrogens. Estrogen receptors (ERs) are subject to alternative splicing, the spliced variants increase following menopause, and they fail to efficiently activate estrogen-dependent signaling pathways. However, the factors that regulate the alternative splicing of ERs remain unknown. We demonstrate novel evidence supporting a potential biological feedback loop where 17ß-estradiol regulates the RNA-binding protein Nova1, which, in turn, regulates the alternative splicing of ERß. These data increase our understanding of ER alternative splicing and could have potential implications for women taking hormone replacement therapy after menopause.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Brain
/
Aging
/
Gene Expression Regulation
/
RNA-Binding Proteins
/
Alternative Splicing
/
Estrogen Receptor beta
/
Estradiol
Limits:
Animals
/
Female
/
Humans
Language:
En
Journal:
Neurobiol Aging
Year:
2018
Document type:
Article
Affiliation country:
United States