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

Publication date: Available online 14 September 2017
Source:Neurobiology of Aging
Author(s): Cody L. Shults, Caitlin B. Dingwall, Chun K. Kim, Elena Pinceti, Yathindar S. Rao, Toni R. Pak
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 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 estrogen receptors remain unknown. We demonstrate novel evidence supporting a potential biological feedback loop where 17β-estradiol regulates the RNA binding protein Nova1, which, in turn, regulates the alternative splicing of estrogen receptor β. These data increase our understanding of estrogen receptor alternative splicing and could have potential implications for women taking hormone replacement therapy post-menopause.



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