Maturation of microRNA is hormonally regulated by a nuclear receptor.
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.
Yamagata
Kaoru
K
Institute of Molecular and Cellular Biosciences, University of Tokyo, Yayoi 1-1-1, Bunkyo-ku, Tokyo 113-0032, Japan.
Fujiyama
Sally
S
Ito
Saya
S
Ueda
Takashi
T
Murata
Takuya
T
Naitou
Masanori
M
Takeyama
Ken-Ichi
K
Minami
Yasuhiro
Y
O'Malley
Bert W
BW
Kato
Shigeaki
S
D020413:3' Untranslated Regions; D000818:Animals; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D004967:Estrogens / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D043244:Ribonuclease III / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
D020413:3' Untranslated Regions; D047628:Estrogen Receptor alpha; D004967:Estrogens; D035683:MicroRNAs; D042461:Vascular Endothelial Growth Factor A; C513400:Drosha protein, mouse; D043244:Ribonuclease III