Non-gonadal PIWI protein, Aubergine, regulates regenerative stem cell proliferation and tumourigenesis in the Drosophila adult intestine.

Somatic stem cells are executors of physiological and pathological proliferation of adult self-renewing tissues, such as the intestine. The actions of intestinal stem cells (ISCs) rely on the integration of cell intrinsic and niche-derived signals, which are necessary to achieve a balanced response to the multiple stimuli that constantly challenge tissue homeostasis and organismal health. Disruption of such balance is causative of age-associated tissue dysfunction and hyperproliferative conditions, including inflammation and cancer. The highly conserved PIWI-interacting RNAs (piRNAs) biosynthesis pathway, also known as the PIWI pathway, has been classically studied in the Drosophila germline for its role in the repression of transposable elements (TEs) and the regulation of germline stem cell homeostasis. Recent reports have emerged on a role of Piwi, the founding member of the pathway, in the maintenance of ISC homeostasis in the adult Drosophila midgut. The implications of these findings regarding a general role of the PIWI pathway and piRNAs in the intestine remain to be addressed. Here, we characterise a cell autonomous role of the PIWI family protein Aubergine (Aub) in ISCs. We show that, while dispensable for homeostatic self-renewal of the midgut, inducible Aub is essential to regulate ISC proliferation following acute damage of the intestinal epithelium and in oncogenic settings. Our work suggests that the role of Aub in ISCs is independent of its piRNAs regulatory function. Instead, Aub drives ISC proliferation through the regulation of protein synthesis, including induction of regenerative stem cell factors Myc and Sox21a, and a parallel pathway involving the eukaryotic initiation factor 3 complex (eIF3). In summary, our results discover a role for Aub in damage-induced proliferation of the adult Drosophila intestine involving the regulation of major regenerative pathways and the protein translation machinery. Furthermore, we present genetically defined hyperplastic settings fostering distinct functions of Aub in intestinal tumourigenesis.