Tsakiri, E., Potiri, M., Kontogiannidi, K., Douka, K., Kanakousaki, K., Vavouraki, N., Loizou, M., Moulos, P., Skoulakis, E.M.C., Samiotaki, M., Kafasla, P., Kiparaki, M. (2026). RpS12-mediated induction of the Xrp1[short] isoform links ribosomal protein mutations to cell competition.  Cell Rep. 45(6): 117380.

FBrf0265721

Research paper

Cell competition, the context-dependent cell elimination phenomenon via short-range cell-cell interactions, was originally described in Drosophila, where heterozygous ribosomal protein (Rp[+/-]) mutant cells are outcompeted by wild-type neighbors. The transcription factor Xrp1 mediates most Rp[+/-] phenotypes, including reduced translation and competitiveness, yet how RpS12 induces Xrp1 was unclear. We show that RpS12 promotes a splice variant of Xrp1 encoding the Xrp1[short] isoform, which defines the Rp[+/-] loser identity. RpS12 overexpression is sufficient to induce Xrp1[short] and confer loser status. Expression of either Xrp1[short] or Xrp1[long] isoform can trigger competition, establishing Xrp1 as the central driver of the loser fate. When the number of losers exceeds a critical threshold, a quorum-like response supports their survival by post-transcriptionally downregulating Xrp1. We identify the RNA-binding protein Syncrip, reduced in Rp[+/-] cells, as an Xrp1 regulator whose depletion activates Xrp1[short]-dependent competition. Therefore, RpS12-dependent Xrp1[short] expression emerges as the primary Rp[+/-] signal initiating cell competition.