期刊
DEVELOPMENTAL CELL
卷 50, 期 6, 页码 716-+出版社
CELL PRESS
DOI: 10.1016/j.devcel.2019.07.026
关键词
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资金
- Johns Hopkins Neuroscience Research Multiphoton Imaging Core [NS050274]
- Johns Hopkins Integrated Imaging Center [S10OD023548]
- JHU SOM Biochemistry, Cellular, and Molecular Biology NIH training grant [T32 GM007445]
- Canadian Institutes of Health Research [PJT156083]
- National Institutes of Health [R37 HD037047]
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 transgenerational silencing of piRNA targets. These observations support a safe harbor model for P granules in protecting germline transcripts from piRNA-initiated silencing.
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