Posttranslational regulation of RNA silencing

RNA silencing is essential for development in all eukaryotes and plays an important role in adaptation to environmental conditions. It is also crucial for the control of transposons. During RNA silencing, the RNase III enzyme Dicer breaks down double-stranded RNA into small RNA of 21 to 24 nucleotides in length. These sRNAs associate with Argonaute (AGO) proteins to form RNA-induced silencing complexes (RISCs). RISCs are programmed by the bound sRNA to interact specifically with transcripts on the basis of sequence complementarity, leading to their downregulation. Despite the obvious importance of RNA silencing in most eukaryotes, little attention has been paid to the molecular mechanisms regulating ARGONAUTE (AGO) protein (and RISC) turnover. Although several ubiquitin E3 ligases have recently been identified that target AGO proteins for selective degradation in Drosophila, mammalian cells and Arabidopsis, their physiological functions are still unknown. In particular, the question of how biotic and abiotic stress factors influence the homeostasis of AGO proteins or RISC at the post-translational level is still largely unresolved. We aim to address this question using the model plant Arabidopsis thaliana. Overall, our studies on the posttranslational control of the AGO1 protein in Arabidopsis are of fundamental importance as they can be transferred to other eukaryotes. The study of AGO1 turnover will also serve as a conceptual approach to understanding critical decision-making in proteolytic pathways.