PT  - JOURNAL ARTICLE
AU  - Thibaut Hacquard
AU  - Marion Clavel
AU  - Patricia Baldrich
AU  - Esther Lechner
AU  - Imma Pérez-Salamó
AU  - Mikhail Schepetilnikov
AU  - Benoît Derrien
AU  - Marieke Dubois
AU  - Philippe Hammann
AU  - Lauriane Kuhn
AU  - Danaé Brun
AU  - Nathalie Bouteiller
AU  - Hervé Vaucheret
AU  - Blake C. Meyers
AU  - Pascal Genschik
TI  - The Arabidopsis F-box protein FBW2 degrades AGO1 to avoid spurious loading of illegitimate small RNA
AID  - 10.1101/2021.03.24.436811
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.03.24.436811
4099  - http://biorxiv.org/content/early/2021/03/24/2021.03.24.436811.short
4100  - http://biorxiv.org/content/early/2021/03/24/2021.03.24.436811.full
AB  - RNA silencing is a conserved mechanism in eukaryotes and is involved in development, heterochromatin maintenance and defense against viruses. In plants, ARGONAUTE1 (AGO1) protein plays a central role in both microRNA (miRNA) and small interfering RNA (siRNA)-directed silencing and its expression is regulated at multiple levels. Here, we report that the F-box protein FBW2 targets proteolysis of AGO1 by a CDC48-mediated mechanism. We found that FBW2 assembles an SCF complex that recognizes the MID-PIWI domain of AGO1 and requires its C-terminal domain containing a GW motif for AGO1 turnover. We showed that FBW2 prefers the unloaded and some mutated forms of AGO1 protein. While FBW2 loss of function does not lead to strong growth or developmental defects, it significantly increases RNA silencing activity. Interestingly, under conditions in which small RNA production or accumulation is affected, the failure to degrade AGO1 in fbw2 mutants becomes more deleterious for the plant. Hence, the non-degradable AGO1 protein assembles high molecular weight complexes and binds illegitimate small RNA leading to the cleavage of new target genes that belong to stress responses and cellular metabolic processes. Therefore, the control of AGO1 homeostasis by ubiquitin ligases plays an important role in quality control to avoid off-target cleavage.Competing Interest StatementThe authors have declared no competing interest.