Format

Send to

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

P Granules Protect RNA Interference Genes from Silencing by piRNAs.

Author information

1
HHMI and Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
2
Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.
3
HHMI and Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: gseydoux@jhmi.edu.

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.

KEYWORDS:

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

PMID:
31402283
PMCID:
PMC6764750
[Available on 2020-09-23]
DOI:
10.1016/j.devcel.2019.07.026

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center