Bellec, KarenCarroll, Lynsey R.Pennel, Kathryn A.F.Tian, YuanliangziYu, YachuanAkan, Aslihan BastemBillard, Caroline V.Doleschall, NoraCameron, Alexander R.Herédia, FabianaGontijo, Alisson M.Ochocka-Fox, Anna M.Blackmur, James P.Din, Farhat V.N.Dunlop, Malcolm G.Edwards, JoanneMyant, KevinHayashi, RippeiCordero, Julia B.2026-04-152026-04-152026-04-282639-1856PURE: 160152194PURE UUID: d3402fe4-c5c9-4295-b4d0-9028160cb273Scopus: 105034676950PubMed: 41894395http://hdl.handle.net/10362/202245Publisher Copyright: © 2026 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license. http://creativecommons.org/licenses/by/4.0/The PIWI-interacting RNA (piRNA) biosynthesis pathway is best studied for its role in suppressing Drosophila germline transposable elements. Piwi, the founding member of the pathway, is involved in adult intestinal stem cell (ISC) homeostasis. Whether a broader role of the PIWI pathway exists in the intestine remains unknown. Here, we characterize a role of the PIWI family protein Aubergine (Aub) in ISCs. While dispensable for basal ISC self-renewal, upregulation of Aub by damage-induced reactive oxygen species drives regenerative ISC proliferation through increased protein synthesis, including translation of ISC factors Myc and Sox21a. Unexpectedly, such roles of Aub in ISCs appear uncoupled from its piRNA regulatory function. Additionally, Aub and mammalian PIWIL1 mediate tumorigenic intestinal growth in Drosophila and human organoids, respectively. Our results reveal regulated protein translation as a fundamental aspect of regenerative ISC function and discover a central role of Aub in such process.13977444engauberginecolorectal cancerCP: cancerCP: stem cell researchDrosophilahuman intestinal organoidsintestinal regenerationintestinal stem cellsPIWIL1protein translationGeneral Biochemistry,Genetics and Molecular BiologySDG 3 - Good Health and Well-beingjournal article10.1016/j.celrep.2026.117186https://www.scopus.com/pages/publications/105034676950