RISCOPHAGY

RNA silencing has become a major focus of molecular research with important implications in medicine, biotechnology and agriculture. In eukaryotes, RNA silencing is crucial for development and plays major roles in response to the environment, including pathogens, as well as in the control of transposable elements. RNA silencing involves processing of double-stranded (ds)RNA by the enzyme Dicer, into small RNA of which one of the two strands is incorporated into a protein complex called RISC (RNA induced silencing complex) that invariably contains a member of the highly conserved ARGONAUTE protein family. Despite the apparent importance of RNA silencing in most eukaryotes, molecular mechanisms regulating ARGONAUTE (AGO) proteins (and RISC) turnover have still received little attention. Although different ubiquitin E3 ligases targeting the selective degradation of AGO proteins have recently been identified in Drosophila, mammalian cells and Arabidopsis, their physiological functions remain still unknown. In particular, how biotic and abiotic stresses regulate the homeostasis of AGO proteins or the RISC at the post-translational level remains largely elusive. Whether RISCs get reprogrammed to adapt to changing conditions and which proteolytic machineries (26S proteasome versus autophagy) mediate RISC homeostasis need further studies. Here, we propose to elucidate these questions in the model plant Arabidopsis thaliana, a multicellular complex eukaryote where the genetic tools and physiological stress responses are readily established. The complementary expertise of Partner P1 (RNA silencing and ubiquitin) and P2 (autophagy) will be instrumental for the success of this proposal. Our findings on RISC homeostasis under stress conditions will fill a fundamental gap in our understanding of RNA silencing process in eukaryotes.