Figure 1

Nuclear receptor regulation of miRNA expression and biogenesis. 1. The miRNA genes are transcribed by RNA polymerase II to produce pri-miRNAs. NRs bind directly to the miRNA gene promoters or interact with other transcription factors that bind to the target miRNA promoters. 2. The pri-miRNAs are cleaved by Drosha and DGCR8 to become pre-miRNAs, which have hairpin-shaped stem-loop structures. ERα inhibits Drosha by direct interaction. 3. The pre-miRNAs are exported to the cytoplasm by Expertin-5 that is induced by estradiol and progestins. 4. The pre-miRNAs undergo further processing by Dicer to become mature miRNAs. The expression of Dicer is increased by estradiol and progestins. 5. The mature miRNAs are loaded to the miRISC to regulate target gene expression. Ago2, a component of the RISC, is induced by estradiol.