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

Fingerprint

Gene Silencing
RNA Interference
Germ Cells
Genes
RNA
Small Interfering RNA
Cells
Mental Competency
Cytoplasm
Ports and harbors
Machinery

Keywords

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

ASJC Scopus subject areas

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

Cite this

Ouyang, J. P. T., Folkmann, A., Bernard, L., Lee, C-Y., Seroussi, U., Charlesworth, A. G., ... Seydoux, G. (2019). P Granules Protect RNA Interference Genes from Silencing by piRNAs. Developmental Cell, 50(6), 716-728.e6. https://doi.org/10.1016/j.devcel.2019.07.026

P Granules Protect RNA Interference Genes from Silencing by piRNAs. / Ouyang, John Paul T.; Folkmann, Andrew; Bernard, Lauren; Lee, Chih-Yung; Seroussi, Uri; Charlesworth, Amanda G.; Claycomb, Julie M.; Seydoux, Geraldine.

In: Developmental Cell, Vol. 50, No. 6, 23.09.2019, p. 716-728.e6.

Research output: Contribution to journalArticle

Ouyang, JPT, Folkmann, A, Bernard, L, Lee, C-Y, Seroussi, U, Charlesworth, AG, Claycomb, JM & Seydoux, G 2019, 'P Granules Protect RNA Interference Genes from Silencing by piRNAs', Developmental Cell, vol. 50, no. 6, pp. 716-728.e6. https://doi.org/10.1016/j.devcel.2019.07.026
Ouyang JPT, Folkmann A, Bernard L, Lee C-Y, Seroussi U, Charlesworth AG et al. P Granules Protect RNA Interference Genes from Silencing by piRNAs. Developmental Cell. 2019 Sep 23;50(6):716-728.e6. https://doi.org/10.1016/j.devcel.2019.07.026
Ouyang, John Paul T. ; Folkmann, Andrew ; Bernard, Lauren ; Lee, Chih-Yung ; Seroussi, Uri ; Charlesworth, Amanda G. ; Claycomb, Julie M. ; Seydoux, Geraldine. / P Granules Protect RNA Interference Genes from Silencing by piRNAs. In: Developmental Cell. 2019 ; Vol. 50, No. 6. pp. 716-728.e6.
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