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 language | English (US) |
|---|---|
| Pages (from-to) | 716-728.e6 |
| Journal | Developmental Cell |
| Volume | 50 |
| Issue number | 6 |
| DOIs | |
| State | Published - Sep 23 2019 |
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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
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 journal › Article
}
TY - JOUR
T1 - P Granules Protect RNA Interference Genes from Silencing by piRNAs
AU - Ouyang, John Paul T.
AU - Folkmann, Andrew
AU - Bernard, Lauren
AU - Lee, Chih-Yung
AU - Seroussi, Uri
AU - Charlesworth, Amanda G.
AU - Claycomb, Julie M.
AU - Seydoux, Geraldine
PY - 2019/9/23
Y1 - 2019/9/23
N2 - 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.
AB - 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.
KW - Argonautes
KW - epigenetic silencing
KW - P granules
KW - piRNAs
KW - RNA-mediated interference
UR - http://www.scopus.com/inward/record.url?scp=85071937367&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85071937367&partnerID=8YFLogxK
U2 - 10.1016/j.devcel.2019.07.026
DO - 10.1016/j.devcel.2019.07.026
M3 - Article
C2 - 31402283
VL - 50
SP - 716-728.e6
JO - Developmental Cell
JF - Developmental Cell
SN - 1534-5807
IS - 6
ER -