P Granules Protect RNA Interference Genes from Silencing by piRNAs

Dev Cell. 2019 Sep 23;50(6):716-728.e6. doi: 10.1016/j.devcel.2019.07.026. Epub 2019 Aug 8.


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.

Keywords: Argonautes; P granules; RNA-mediated interference; epigenetic silencing; piRNAs.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans / embryology
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans Proteins / metabolism
  • Cell Nucleus / metabolism
  • Cytoplasmic Granules / genetics*
  • Embryo, Nonmammalian / metabolism
  • Epigenesis, Genetic
  • Genes, Helminth
  • Genetic Loci
  • Germ Cells / metabolism
  • Models, Biological
  • Mutation / genetics
  • Phenotype
  • RNA Interference*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / genetics*
  • RNA, Small Interfering / metabolism
  • Transcription, Genetic
  • Up-Regulation / genetics


  • Caenorhabditis elegans Proteins
  • RNA, Messenger
  • RNA, Small Interfering