17beta-estradiol regulates the RNA-binding protein Nova1, which then regulates the alternative splicing of estrogen receptor beta in the aging female rat brain Journal Article


Authors: Shults, C. L.; Dingwall, C. B.; Kim, C. K.; Pinceti, E.; Rao, Y. S.; Pak, T. R.
Article Title: 17beta-estradiol regulates the RNA-binding protein Nova1, which then regulates the alternative splicing of estrogen receptor beta in the aging female rat brain
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 17beta-estradiol regulates the RNA-binding protein Nova1, which, in turn, regulates the alternative splicing of ERbeta. These data increase our understanding of ER alternative splicing and could have potential implications for women taking hormone replacement therapy after menopause.
Keywords: Aging; Alternative Splicing; Brain; Estrogen receptor beta; Nova1
Journal Title: Neurobiology of aging
Volume: 61
ISSN: 1558-1497; 0197-4580
Publisher: Elsevier Inc  
Journal Place: United States
Date Published: 2018
Start Page: 13
End Page: 22
Language: eng
DOI/URL:
Notes: LR: 20171219; CI: Copyright (c) 2017; GR: R01 AG033605/AG/NIA NIH HHS/United States; JID: 8100437; NIHMS906047; OTO: NOTNLM; PMCR: 2019/01/01 00:00; 2017/04/10 00:00 [received]; 2017/09/05 00:00 [revised]; 2017/09/06 00:00 [accepted]; 2019/01/01 00:00 [pmc-release]; 2017/10/17 06:00 [pubmed]; 2017/10/17 06:00 [medline]; 2017/10/15 06:00 [entrez]; ppublish