TRBP, a regulator of cellular PKR and HIV-1 virus expression, interacts with Dicer and functions in RNA silencing.

EMBO reports ·Vol. 6 ·No. 10 ·2005-10-00 ·Pages 961-7

Haase AD, Jaskiewicz L, Zhang H, Lainé S, Sack R, Gatignol A, Filipowicz W

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.

MeSH Terms

Cell Line Gene Expression Regulation, Viral Genes, Regulator HIV Long Terminal Repeat HIV-1/genetics Humans Immunoprecipitation Interferons MicroRNAs/biosynthesis,metabolism RNA Interference/physiology RNA, Small Interfering/biosynthesis,metabolism RNA-Binding Proteins/genetics,metabolism RNA-Induced Silencing Complex Ribonuclease III/genetics,metabolism Trans-Activators eIF-2 Kinase/genetics

Chemicals

MicroRNAs RNA, Small Interfering RNA-Binding Proteins RNA-Induced Silencing Complex Trans-Activators trans-activation responsive RNA-binding protein Interferons eIF-2 Kinase Ribonuclease III

Authors & Affiliations

7 authors, click to expand affiliations / ORCID

Haase Astrid D

Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4508 Basel, Switzerland.

Jaskiewicz Lukasz

Zhang Haidi

Lainé Sébastien

Sack Ragna

Gatignol Anne

Filipowicz Witold

References (24)

24 references, click to expand

TRBP recruits the Dicer complex to Ago2 for microRNA processing and gene silencing.
Nature. 2005 Aug 4;436(7051):740-4 PMID: 15973356
Normal microRNA maturation and germ-line stem cell maintenance requires Loquacious, a double-stranded RNA-binding domain protein.
PLoS Biol. 2005 Jul;3(7):e236 PMID: 15918770
Two dimerization domains in the trans-activation response RNA-binding protein (TRBP) individually reverse the protein kinase R inhibition of HIV-1 long terminal repeat expression.
J Biol Chem. 2001 Sep 7;276(36):33899-905 PMID: 11438532
Organization of the human tarbp2 gene reveals two promoters that are repressed in an astrocytic cell line.
J Biol Chem. 2001 Dec 28;276(52):48803-13 PMID: 11641396
The TAR RNA-binding protein, TRBP, stimulates the expression of TAR-containing RNAs in vitro and in vivo independently of its ability to inhibit the dsRNA-dependent kinase PKR.
J Biol Chem. 2003 Feb 14;278(7):4440-8 PMID: 12475984
R2D2, a bridge between the initiation and effector steps of the Drosophila RNAi pathway.
Science. 2003 Sep 26;301(5641):1921-5 PMID: 14512631
The carboxy-terminal, M3 motifs of PACT and TRBP have opposite effects on PKR activity.
Virology. 2003 Oct 25;315(2):283-91 PMID: 14585331
Dicer is essential for mouse development.
Nat Genet. 2003 Nov;35(3):215-7 PMID: 14528307
Characterization of the interactions between mammalian PAZ PIWI domain proteins and Dicer.
EMBO Rep. 2004 Feb;5(2):189-94 PMID: 14749716
Merlin, a tumor suppressor, interacts with transactivation-responsive RNA-binding protein and inhibits its oncogenic activity.
J Biol Chem. 2004 Jul 16;279(29):30265-73 PMID: 15123692
Oligomerization activity of a double-stranded RNA-binding domain.
FEBS Lett. 2004 Sep 10;574(1-3):25-30 PMID: 15358534
Serine 18 phosphorylation of RAX, the PKR activator, is required for PKR activation and consequent translation inhibition.
J Biol Chem. 2004 Oct 8;279(41):42687-93 PMID: 15299031
Characterization of a human TAR RNA-binding protein that activates the HIV-1 LTR.
Science. 1991 Mar 29;251(5001):1597-600 PMID: 2011739
Oncogenic potential of TAR RNA binding protein TRBP and its regulatory interaction with RNA-dependent protein kinase PKR.
EMBO J. 1997 Feb 3;16(3):611-24 PMID: 9034343
A double-stranded RNA binding protein required for activation of repressed messages in mammalian germ cells.
Nat Genet. 1999 Jun;22(2):171-4 PMID: 10369260
A protein sensor for siRNA asymmetry.
Science. 2004 Nov 19;306(5700):1377-80 PMID: 15550672
RNAi-mediated pathways in the nucleus.
Nat Rev Genet. 2005 Jan;6(1):24-35 PMID: 15630419
Perspective: machines for RNAi.
Genes Dev. 2005 Mar 1;19(5):517-29 PMID: 15741316
Evidence that HIV-1 encodes an siRNA and a suppressor of RNA silencing.
Immunity. 2005 May;22(5):607-19 PMID: 15894278
Functional genomic analysis of RNA interference in C. elegans.
Science. 2005 May 20;308(5725):1164-7 PMID: 15790806
The RISC subunit Tudor-SN binds to hyper-edited double-stranded RNA and promotes its cleavage.
Nat Struct Mol Biol. 2005 Jun;12(6):489-96 PMID: 15895094
MicroRNA biogenesis: coordinated cropping and dicing.
Nat Rev Mol Cell Biol. 2005 May;6(5):376-85 PMID: 15852042
Processing of pre-microRNAs by the Dicer-1-Loquacious complex in Drosophila cells.
PLoS Biol. 2005 Jul;3(7):e235 PMID: 15918769
A link between RNA interference and nonsense-mediated decay in Caenorhabditis elegans.
Science. 2000 Sep 15;289(5486):1928-31 PMID: 10988072

Article Info

Journal

EMBO reports

Abbr.

EMBO Rep

ISSN

1469-221X

DOI

10.1038/sj.embor.7400509

Published

2005-10-00

Pages

961-7

Language

English

Region

England

NLM ID

100963049

PMCID

PMC1369185

Subset

External Links

PubMed source DOI: 10.1038/sj.embor.7400509 PMC Full Text View journal details

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TRBP, a regulator of cellular PKR and HIV-1 virus expression, interacts with Dicer and functions in RNA silencing.

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