Maternal piRNAs Are Essential for Germline Development following De Novo Establishment of Endo-siRNAs in Caenorhabditis elegans.

The Piwi-piRNA pathway represents a germline-specific transposon-defense system. C. elegans Piwi, prg-1, is a non-essential gene and triggers a secondary RNAi response that depends on mutator genes, endo-siRNAs (22G-RNAs), and the 22G-RNA-binding Argonaute protein HRDE-1. Interestingly, silencing of PRG-1 targets can become PRG-1 independent. This state, known as RNAe, is heritable and depends on mutator genes and HRDE-1. We studied how the transgenerational memory of RNAe and the piRNA pathway interact. We find that maternally provided PRG-1 is required for de novo establishment of 22G-RNA populations, especially those targeting transposons. Strikingly, attempts to re-establish 22G-RNAs in absence of both PRG-1 and RNAe memory result in severe germline proliferation defects. This is accompanied by a disturbed balance between gene-activating and -repressing 22G-RNA pathways. We propose a model in which CSR-1 prevents the loading of HRDE-1 and in which both PRG-1 and HRDE-1 help to keep mutator activity focused on the proper targets.