Argonaute quenching and global changes in Dicer homeostasis caused by a pathogen-encoded GW repeat protein
- Jacinthe Azevedo1,
- Damien Garcia1,
- Dominique Pontier2,
- Stephanie Ohnesorge1,
- Agnes Yu1,
- Shahinez Garcia1,
- Laurence Braun3,
- Marc Bergdoll1,
- Mohamed Ali Hakimi3,
- Thierry Lagrange2 and
- Olivier Voinnet1,4,5
- 1Institut de Biologie Moléculaire des Plantes du CNRS, Université de Strasbourg, 67084 Strasbourg Cedex, France;
- 2Laboratoire Génome et Développement des Plantes, Centre National de la Recherche Scientifique/Institut de Recherche et Développement/Université de Perpignan, 66860 Perpignan, France;
- 3Laboratoire Adaptation et Pathogénie des Micro-organismes, CNRS UMR, F-38042 Grenoble Cedex 9, France
Abstract
In plants and invertebrates, viral-derived siRNAs processed by the RNaseIII Dicer guide Argonaute (AGO) proteins as part of antiviral RNA-induced silencing complexes (RISC). As a counterdefense, viruses produce suppressor proteins (VSRs) that inhibit the host silencing machinery, but their mechanisms of action and cellular targets remain largely unknown. Here, we show that the Turnip crinckle virus (TCV) capsid, the P38 protein, acts as a homodimer, or multiples thereof, to mimic host-encoded glycine/tryptophane (GW)-containing proteins normally required for RISC assembly/function in diverse organisms. The P38 GW residues bind directly and specifically to Arabidopsis AGO1, which, in addition to its role in endogenous microRNA-mediated silencing, is identified as a major effector of TCV-derived siRNAs. Point mutations in the P38 GW residues are sufficient to abolish TCV virulence, which is restored in Arabidopsis ago1 hypomorphic mutants, uncovering both physical and genetic interactions between the two proteins. We further show how AGO1 quenching by P38 profoundly impacts the cellular availability of the four Arabidopsis Dicers, uncovering an AGO1-dependent, homeostatic network that functionally connects these factors together. The likely widespread occurrence and expected consequences of GW protein mimicry on host silencing pathways are discussed in the context of innate and adaptive immunity in plants and metazoans.
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Footnotes
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↵4 Address as of November 2010: Swiss Federal Institute of Technology (ETH), 8092 Zurich, Switzerland.
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↵5 Corresponding author.
E-MAIL olivier.voinnet{at}ibmp-ulp.u-strasbg.fr; FAX 33-03-88417158.
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Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.1908710.
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Supplemental material is available at http://www.genesdev.org.
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- Received January 22, 2010.
- Accepted March 15, 2010.
- Copyright © 2010 by Cold Spring Harbor Laboratory Press