title: RNA-induced silencing complex (RISC) Proteins PACT, TRBP, and Dicer are SRA binding nuclear receptor coregulators.
abstract: The 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.
authors.affiliation: Laboratory for Cancer Medicine, University of Western Australia Centre for Medical Research, Western Australian Institute for Medical Research, Perth, WA, Australia.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Redfern
authors.forename: Shane M
authors.initials: SM
authors.lastname: Colley
authors.forename: Dianne J
authors.initials: DJ
authors.lastname: Beveridge
authors.forename: Naoya
authors.initials: N
authors.lastname: Ikeda
authors.forename: Michael R
authors.initials: MR
authors.lastname: Epis
authors.forename: Xia
authors.initials: X
authors.lastname: Li
authors.forename: Charles E
authors.initials: CE
authors.lastname: Foulds
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Stuart
authors.forename: Andrew
authors.initials: A
authors.lastname: Barker
authors.forename: Victoria J
authors.initials: VJ
authors.lastname: Russell
authors.forename: Kerry
authors.initials: K
authors.lastname: Ramsay
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Kobelke
authors.forename: Xiaotao
authors.initials: X
authors.lastname: Li
authors.forename: Esme C
authors.initials: EC
authors.lastname: Hatchell
authors.forename: Christine
authors.initials: C
authors.lastname: Payne
authors.forename: Keith M
authors.initials: KM
authors.lastname: Giles
authors.forename: Adriana
authors.initials: A
authors.lastname: Messineo
authors.forename: Anne
authors.initials: A
authors.lastname: Gatignol
authors.forename: Rainer B
authors.initials: RB
authors.lastname: Lanz
authors.forename: Bert W
authors.initials: BW
authors.lastname: O'Malley
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Leedman
mesh_terms: D015153:Blotting, Western; D002352:Carrier Proteins / Q000378:metabolism*; D002458:Cell Fractionation; D047369:Chromatin Immunoprecipitation; D003001:Cloning, Molecular; D053487:DEAD-box RNA Helicases / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000235:genetics*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008156:Luciferases; D061986:MCF-7 Cells; D035683:MicroRNAs / Q000378:metabolism*; D010957:Plasmids / Q000235:genetics; D034622:RNA Interference; D016601:RNA-Binding Proteins / Q000378:metabolism*; D034743:RNA-Induced Silencing Complex / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D043244:Ribonuclease III / Q000378:metabolism*; D014162:Transfection; D020798:Two-Hybrid System Techniques; D000099253:Trans-Activation Responsive RNA-Binding Protein
chemical_list: D002352:Carrier Proteins; D053487:DEAD-box RNA Helicases; D008156:Luciferases; D035683:MicroRNAs; D016601:RNA-Binding Proteins; D034743:RNA-Induced Silencing Complex; D043244:Ribonuclease III; D000099253:Trans-Activation Responsive RNA-Binding Protein; C104647:PRKRA protein, human; C548898:steroid receptor RNA activator, human; C408087:DICER1 protein, human
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