Maturation of MicroRNA Is Hormonally Regulated by a Nuclear Receptor

• DOI: 10.1016/j.molcel.2010.02.011
• Publication Date: 2010-02-26T05:37:47Z
• Authors: Kaoru Yamagata; Sally Fujiyama; Saya Ito; Takashi Ueda; Takuya Murata; Masanori Naitou; Ken-ichi Takeyama; Yasuhiro Minami; Bert W. O'Malley; Shigeaki Kato
• Keywords: Ribonuclease III; Vascular Endothelial Growth Factor A; 0303 health sciences; Estrogen Receptor alpha; Down-Regulation; Estrogens; Cell Biology; Mice; MicroRNAs; 03 medical and health sciences; Cell Line, Tumor; Animals; Humans; Molecular Biology; 3' Untranslated Regions

Steroid hormones and their cognate nuclear receptors exert a wide spectrum of biological actions through regulation of transcriptional and posttranscriptional processes. However, the underlying molecular mechanism by which steroid hormones control posttranscriptional processes is largely unknown. We now report that estrogen receptor alpha (ERalpha) inhibits the maturation of a particular microRNA (miRNA) and thereby stabilizes the mRNA of an ERalpha target gene through the 3'UTR. Estrogen-bound ERalpha downregulated expression of a set of miRNAs in both animals and cultured cells. Activated ERalpha attenuated the processing of primary miRNAs into pre-miRNAs through estrogen-dependent association with the Drosha complex, resulting in stabilization of the transcript of an ERalpha target gene through its 3'UTR. Thus, a steroid hormone achieves posttranscriptional control by regulating the maturation of miRNA.