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Title

Regulation of Nuclear Receptor Expression by miRNAs

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Director
Denomination Master en biologie
Defense Maîtrise : Univ. Genève, 2011
Abstract The nuclear receptor superfamily includes steroid hormone receptors (SHR), which are activated by hormones and regulate many key physiological processes. However, their deregulation is implicated in a variety of pathological disorders and diseases, including many types of cancer. MicroRNAs are non-conding RNAs of about 20-25 nucleotides and in the recent years, they have come to represent a major layer of regulation of gene expression, contributing to regulation of many physiological processes in a vast number of eukaryotic organisms. In metazoans, microRNAs regulate the gene expression mainly through the partial sequence complementarity present in the 3ʼUTR of the target mRNA. MicroRNAs are typically known to repress expression of their target genes, however in some cases, they are shown to upregulate gene expression. Whereas there is a plethora of literature for miRNA mediated repression of gene expression, upregulation mediated by miRNAs is quite poorly studied with only a few examples described. Here we report that miR-219 is potentially involved in upregulation of the estrogen receptor alpha (ERα) expression. Furthermore, our results indicate that this phenomenon may involve FXR1 and AUF1p45, proteins known to be involved in RNA metabolism. In the second part of this study, we focus on another SHR, Glucocorticoid receptor (GR). The 3ʼUTR of GR mRNA harbours target sites for many miRNAs. We tested several of them and found that miR-22 directly targets the 3ʼUTR of GR mRNA at two distinct sites and represses GR expression.
Keywords MiRNAsEstrogen receptorBreast cancerGlucocorticoid receptorGene expression
Stable URL https://archive-ouverte.unige.ch/unige:15729
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Deposited on : 2011-05-06

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