RNA-induced Silencing Complex (RISC) Proteins PACT, TRBP, and Dicer Are SRA Binding Nuclear Receptor Coregulators

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2013 Apr 4

PMID 23550157

Citations 56

Authors

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 OMalley

Peter J Leedman

Affiliations

Soon will be listed here.

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.

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