Post-transcriptional effects of estrogens on gene expression: Messenger RNA stability and translation regulated by micrornas and other factors
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Estrogens exert powerful effects on physiology by regulating gene expression. Their effects on the transcriptional activities of genes are well described in the literature. However, estrogens are also the hormones that are best known for post-transcriptional gene regulation. With the combination of transcriptional and post-transcriptional regulation, gene expression can be rapidly and powerfully controlled to maximize the utility of genomic information throughout the long lives of vertebrate animals. For some cell responses, up to 50% of the genes with altered expression are the result of changes in the stabilities of the messenger RNAs (mRNAs). For many genes including the estrogen receptor alpha (ER) gene, post-transcriptional regulation is the primary mode of alteration of expression. This indicates that post-transcriptional gene regulation is critical to estrogen actions because the ER protein determines the estrogen-responsiveness of animal tissues to a large extent. Estrogens have been shown to regulate the expression of certain genes by greatly altering the stabilities of mRNAs, including stabilizing ER mRNA. This effect may be ancient as it appears to be conserved from mammals to fish and frogs. Some studies have identified unique proteins that are induced by estrogens to bind and protect specific mRNAs from degradation. Recently, hundreds of microRNAs have been discovered and are estimated to actively regulate about one third of protein-encoding mRNAs. MicroRNAs associate with proteins in complexes on mRNAs, where they usually destabilize the mRNA or block its translation. Estrogens regulate the expression of microRNA genes in responsive tissues during normal physiology and disease processes. Other cell signals alter the expression of certain microRNAs that affect ER gene expression. Elucidation of the molecular mechanisms responsible for these post-transcriptional effects is certain to reveal novel molecular targets for therapeutic control of estrogen actions. © 2012 by Nova Science Publishers, Inc. All rights reserved.
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Estrogens: Biochemistry, Therapeutic Uses and Physiological Effects