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Argonaute quenching and global changes in Dicer homeostasis caused by a pathogen-encoded GW repeat protein.

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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Contributor : Elisabeth Goetschy Connect in order to contact the contributor
Submitted on : Wednesday, February 13, 2013 - 5:14:55 PM
Last modification on : Sunday, April 17, 2022 - 3:26:31 AM

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Jacinthe Azevedo, Damien Garcia, Dominique Pontier, Stephanie Ohnesorge, Agnes Yu, et al.. Argonaute quenching and global changes in Dicer homeostasis caused by a pathogen-encoded GW repeat protein.. Genes and Development, Cold Spring Harbor Laboratory Press, 2010, 24 (9), pp.904-15. ⟨10.1101/gad.1908710⟩. ⟨hal-00788111⟩



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