Daedalus and Gasz recruit Armitage to mitochondria, bringing piRNA precursors to the biogenesis machinery

The piRNA pathway is a small RNA-based immune system that silences mobile genetic elements in animal germlines. piRNA biogenesis requires a specialised machinery that converts long single-stranded precursors into small RNAs of ~25-nucleotides in length. This process involves factors that operate in two different subcellular compartments: the nuage/Yb-body and mitochondria. How these two sites communicate to achieve accurate substrate selection and efficient processing remains unclear. Here, we investigate a previously uncharacterized piRNA biogenesis factor, Daedalus (Daed), that is located on the outer mitochondrial membrane. Daed is essential for Zucchini-mediated piRNA production and for the correct localisation of the indispensable piRNA biogenesis factor Armitage (Armi). We find that Gasz and Daed interact with each other and likely provide a mitochondrial “anchoring platform” to ensure that Armi is held in place, proximal to Zucchini, during piRNA precursor processing. Our data suggest that Armi initially identifies piRNA precursors in nuage/Yb-body in a manner that depends upon Piwi and then moves to mitochondria to present them to the biogenesis machinery. These results represent a significant step in understanding a critical aspect of transposon silencing, namely how RNAs are chosen to instruct the piRNA machinery in the nature of its silencing targets. Characterization of newly discovered Drosophila melanogaster gene CG10880 (Daedalus) involvement in piRNA biogenesis smallRNA seq: OSCs were treated with indicated siRNA CLIPseq: OSCs were treated with siRNA and transfected with indicated plasmids