• Andrew D Redfern, Shane M Colley, Dianne J Beveridge, Naoya Ikeda, Michael R Epis, Xia Li, Charles E Foulds, Lisa M Stuart, Andrew Barker, Victoria J Russell, Kerry Ramsay, Simon J Kobelke, Xiaotao Li, Esme C Hatchell, Christine Payne, Keith M Giles, Adriana Messineo, Anne Gatignol, Rainer B Lanz, Bert W O'Malley, and Peter J Leedman.
• Laboratory for Cancer Medicine, University of Western Australia Centre for Medical Research, Western Australian Institute for Medical Research, Perth, WA, Australia.
• Proc. Natl. Acad. Sci. U.S.A. 2013 Apr 16;110(16):6536-41.

AbstractThe cytoplasmic RNA-induced silencing complex (RISC) contains dsRNA binding proteins, including protein kinase RNA activator (PACT), transactivation response RNA binding protein (TRBP), and Dicer, that process pre-microRNAs into mature microRNAs (miRNAs) that target specific mRNA species for regulation. There is increasing evidence for important functional interactions between the miRNA and nuclear receptor (NR) signaling networks, with recent data showing that estrogen, acting through the estrogen receptor, can modulate initial aspects of nuclear miRNA processing. Here, we show that the cytoplasmic RISC proteins PACT, TRBP, and Dicer are steroid receptor RNA activator (SRA) binding NR coregulators that target steroid-responsive promoters and regulate NR activity and downstream gene expression. Furthermore, each of the RISC proteins, together with Argonaute 2, associates with SRA and specific pre-microRNAs in both the nucleus and cytoplasm, providing evidence for links between NR-mediated transcription and some of the factors involved in miRNA processing.

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