RRC ID 59571
Author Ouyang JPT, Folkmann A, Bernard L, Lee CY, Seroussi U, Charlesworth AG, Claycomb JM, Seydoux G.
Title P Granules Protect RNA Interference Genes from Silencing by piRNAs.
Journal Dev Cell
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.
Volume 50(6)
Pages 716-728.e6
Published 2019-9-23
DOI 10.1016/j.devcel.2019.07.026
PII S1534-5807(19)30632-X
PMID 31402283
PMC PMC6764750
MeSH 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
IF 9.19
Times Cited 8
C.elegans tm1200 tm1019 tm892