Transgenerational sterility of small RNA genome silencing mutants in response to germ granule dysfunction

Abstract

In several species, Piwi/piRNA genome silencing defects lead to immediate sterility accompanied by heterochromatin dysfunction and transposon-induced genomic instability, which may cause Piwi mutant sterility. In C. elegans, Piwi pathway mutants transmit a heritable stress through germ cells that induces sterility after growth for several generations. We found that sterile Piwi pathway mutant germ cells displayed inconsistent increases in DNA damage but consistently altered perinuclear germ granules that are known to promote fertility. Germ granule dysfunction did not elicit transposon expression but was sufficient to induce multiple phenotypes found in sterile Piwi silencing mutants, including germline atrophy and regrowth. Furthermore, loss of the germ granule component PGL-1 accelerated sterility in response to deficiency for prg-1/Piwi. Restoration of germ granule function to sterile pgl-1 mutants restored their fertility. Together, our results suggest that germ granule defects may promote an adult reproductive arrest phenotype that is responsible for Piwi/piRNA mutant sterility.