TRBP, a Regulator of Cellular PKR and HIV-1 Virus Expression, Interacts with Dicer and Functions in RNA Silencing

Overview

Journal EMBO Rep

Specialty Molecular Biology

Date 2005 Sep 6

PMID 16142218

Citations 343

Authors

Astrid D Haase

Lukasz Jaskiewicz

Haidi Zhang

Sebastien Laine

Ragna Sack

Anne Gatignol

Witold Filipowicz

Affiliations

Soon will be listed here.

Abstract

Dicer is a key enzyme involved in RNA interference (RNAi) and microRNA (miRNA) pathways. It is required for biogenesis of miRNAs and small interfering RNAs (siRNAs), and also has a role in the effector steps of RNA silencing. Apart from Argonautes, no proteins are known to associate with Dicer in mammalian cells. In this work, we describe the identification of TRBP (human immunodeficiency virus (HIV-1) transactivating response (TAR) RNA-binding protein) as a protein partner of human Dicer. We show that TRBP is required for optimal RNA silencing mediated by siRNAs and endogenous miRNAs, and that it facilitates cleavage of pre-miRNA in vitro. TRBP had previously been assigned several functions, including inhibition of the interferon-induced double-stranded RNA-regulated protein kinase PKR and modulation of HIV-1 gene expression by association with TAR. The TRBP-Dicer interaction shown raises interesting questions about the potential interplay between RNAi and interferon-PKR pathways.

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