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 journalArticle

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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