17β-estradiol regulates the RNA-binding protein Nova1, which then regulates the alternative splicing of estrogen receptor β in the aging female rat brain
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 dem...
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| Published in | Neurobiology of aging Vol. 61; pp. 13 - 22 |
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| Main Authors | , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
Elsevier Inc
01.01.2018
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| Subjects | |
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| 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 17β-estradiol regulates the RNA-binding protein Nova1, which, in turn, regulates the alternative splicing of ERβ. These data increase our understanding of ER alternative splicing and could have potential implications for women taking hormone replacement therapy after menopause. |
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| AbstractList | 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 17β-estradiol regulates the RNA-binding protein Nova1, which, in turn, regulates the alternative splicing of ERβ. These data increase our understanding of ER alternative splicing and could have potential implications for women taking hormone replacement therapy after menopause. 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. |
| Author | Dingwall, Caitlin B. Kim, Chun K. Pak, Toni R. Rao, Yathindar S. Shults, Cody L. Pinceti, Elena |
| Author_xml | – sequence: 1 givenname: Cody L. surname: Shults fullname: Shults, Cody L. – sequence: 2 givenname: Caitlin B. surname: Dingwall fullname: Dingwall, Caitlin B. – sequence: 3 givenname: Chun K. surname: Kim fullname: Kim, Chun K. – sequence: 4 givenname: Elena surname: Pinceti fullname: Pinceti, Elena – sequence: 5 givenname: Yathindar S. surname: Rao fullname: Rao, Yathindar S. – sequence: 6 givenname: Toni R. orcidid: 0000-0002-9685-9754 surname: Pak fullname: Pak, Toni R. email: tpak@luc.edu |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/29031089$$D View this record in MEDLINE/PubMed |
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| CitedBy_id | crossref_primary_10_1016_j_omtn_2020_09_040 crossref_primary_10_7717_peerj_13446 crossref_primary_10_3390_ncrna9060074 crossref_primary_10_1186_s40164_018_0116_7 crossref_primary_10_3390_ani14020251 crossref_primary_10_3389_fphar_2019_00140 crossref_primary_10_3389_fendo_2021_692677 |
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| SubjectTerms | Aging Aging - genetics Aging - metabolism Alternative splicing Alternative Splicing - genetics Animals Brain Brain - metabolism Cells, Cultured Estradiol - physiology Estrogen Receptor beta - genetics Estrogen Receptor beta - metabolism Estrogen receptor β Female Gene Expression Regulation Humans Nova1 Rats, Inbred F344 RNA-Binding Proteins - physiology |
| Title | 17β-estradiol regulates the RNA-binding protein Nova1, which then regulates the alternative splicing of estrogen receptor β in the aging female rat brain |
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