TY - JOUR T1 - DAF-16/Foxo suppresses the transgenerational sterility of <em>prg-1</em> piRNA mutants via a systemic small RNA pathway JF - bioRxiv DO - 10.1101/326751 SP - 326751 AU - Matt Simon AU - Maya Spichal AU - Bree Heestand AU - Stephen Frenk AU - Ashley Hedges AU - Malik Godwin AU - Alicia S. Wellman AU - Aisa Sakaguchi AU - Shawn Ahmed Y1 - 2018/01/01 UR - http://biorxiv.org/content/early/2018/05/20/326751.abstract N2 - Mutation of the daf-2 insulin/IGF-1 receptor activates the DAF-16/Foxo transcription factor to suppress the transgenerational sterility phenotype of prg-1/piRNA mutants that are deficient for piRNA-mediated genome silencing. As with PRG-1/piRNAs, mutations in the nuclear RNA interference gene nrde-1 compromised germ cell immortality, but deficiency for daf-2 did not suppress the transgenerational sterility of nrde-1 or nrde-4 single mutants or of prg-1; nrde-4 or prg-1; hrde-1 double mutants. NRDE-1 and NRDE-4 promote transcriptional silencing in somatic cells via the nuclear Argonaute protein NRDE-3, which was dispensable for germ cell immortality. However, daf-2 deficiency failed to promote germ cell immortality in prg-1; nrde-3 mutants. Consistently, we found that DAF-16 activity in somatic cells suppressed the transgenerational sterility of prg-1 mutants via the SID-1 dsRNA transmembrane channel that promotes systemic RNAi as well as Dicer, the dsRNA binding protein RDE-4 and the RDRP RRF-3. We conclude that DAF-16 activates a cell-non-autonomous systemic RNAi pathway that promotes small RNA-mediated genome silencing in germ cells to suppress loss of the genomic immune surveillance factor Piwi/PRG-1. ER -