P Granules Protect RNA Interference Genes from Silencing by piRNAs

John Paul T. Ouyang, Andrew Folkmann, Lauren Bernard, Chih-Yung Lee, Uri Seroussi, Amanda G. Charlesworth, Julie M. Claycomb, Geraldine Seydoux

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

P 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 and 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.

Original languageEnglish (US)
Pages (from-to)716-728.e6
JournalDevelopmental Cell
Volume50
Issue number6
DOIs
StatePublished - Sep 23 2019

Keywords

  • Argonautes
  • P granules
  • RNA-mediated interference
  • epigenetic silencing
  • piRNAs

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

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