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

Marzia Munafò, Vera Manelli, Federica A Falconio, Ashley Sawle, Emma Kneuss, Evelyn L Eastwood, Jun Wen Eugene Seah, Benjamin Czech, Gregory J Hannon

OAI: oai:www.repository.cam.ac.uk:1810/293203 • DOI: 10.17863/CAM.40351

The Piwi-interacting RNA (piRNA) pathway is a small RNA-based immune system that silences mobile genetic elements in animal germlines. piRNA biogenesis requires a specialized machinery that converts long singlestranded 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 the correct localization of the indispensable piRNA biogenesis factor Armitage (Armi). We found 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 processing. Our data suggest that Armi initially identifies piRNA precursors in nuage/Yb bodies in a manner that depends on Piwi and then moves to mitochondria to present precursors to the mitochondrial 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.

Drosophila PIWI proteins Mitochondria Ovary piRNA biogenesis transposon Animals Cell Line Drosophila Proteins Drosophila melanogaster Gene Knockdown Techniques Membrane Proteins Mitochondria Protein Binding Protein Transport RNA Helicases RNA Small Interfering