In this study, Kim et al. set out to elucidate the molecular details of how PIWI proteins in planarian flatworms contribute to stem cell function and regeneration. Using novel biochemical tools, such as IP-seq, ribodepletion, HITS-CLIP, and SHAPE-MaP, the authors show that PIWI proteins enable planarians to repurpose piRNAs for critical roles in neoblast mRNA turnover.