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bioRxiv · 10.1101/707562

P granules protect RNA interference genes from silencing by piRNAs

Ouyang, J. P.·Folkmann, A.·Bernard, L.·Lee, C.-Y.·Seroussi, U.·Charlesworth, A. G.·Claycomb, J. M.·Seydoux, G.
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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, 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.

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Ouyang, J. P., Folkmann, A., Bernard, L., Lee, C.-Y., Seroussi, U., Charlesworth, A. G., Claycomb, J. M., Seydoux, G.. 2019-07-18. P granules protect RNA interference genes from silencing by piRNAs. https://doi.org/10.1101/707562

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