Thomas Liontis, Alla Grishok
Small interfering RNAs bound to Argonautes ALG-3 and ALG-4 ( ALG-3 /4) in spermatocytes regulate fertility and aging in C. elegans . ALG-3 /4 cell non-autonomously repress DAF-18 /PTEN in the oocyte, thereby limiting the activity of DAF-16 /FOXO and longevity. We find that the DAF-16 and ALG-3 /4 target gene lea-1 is downregulated in precursor germ cells and oocytes of alg-3 /4 mutants while being upregulated in age-1 ( hx546 ) PI3K mutants, where DAF-16 is activated. The downregulation of lea-1 in alg-3 /4 mutants is inherited, unlike the elevation in DAF-18 levels. We therefore propose that ALG-3 /4 regulate LEA-1 and DAF-18 through distinct non-autonomous mechanisms.