P Granules Protect RNA Interference Genes from Silencing by piRNAs

• DOI: 10.1016/j.devcel.2019.07.026
• Publication Date: 2019-08-08T14:43:17Z
• Authors: John Paul T. Ouyang; Andrew Folkmann; Lauren Bernard; Chih-Yung Lee; Uri Seroussi; Amanda G. Charles...; Julie M. Claycomb; Geraldine Seydoux
• Keywords: Piwi-interacting RNA; Argonaute; RasiRNA; RNA-induced silencing complex; Trans-acting siRNA; RNA Silencing

SUMMARYP granules are perinuclear condensates in C. elegans germ cells proposed to serve as hubs for self/non-self RNA discrimination by Argonautes. We report that a mutant (meg-3 meg-4) that does not assemble P granules in primordial germ cells loses competence for RNA-interference over several generations and accumulates silencing small RNAs against hundreds of endogenous genes, including the RNA-interference genes rde-11 and sid-1. In wild-type, rde-11 and sid-1 transcripts are heavily targeted by piRNAs, accumulate in P granules, but maintain expression. In the primordial germ cells of meg-3 meg-4 mutants, rde-11 and sid-1 transcripts disperse in the cytoplasm with the small RNA biogenesis machinery, become hyper-targeted by secondary sRNAs, and are eventually silenced. Silencing requires the PIWI-class Argonaute PRG-1 and the nuclear Argonaute HRDE-1 that maintains trans-generational silencing of piRNA targets. These observations support a “safe harbor” model for P granules in protecting germline transcripts from piRNA-initiated silencing.