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DAF-16/Foxo suppresses the transgenerational sterility of prg-1 piRNA mutants via a systemic small RNA pathway

Matt Simon, Maya Spichal, Bree Heestand, Stephen Frenk, Ashley Hedges, Malik Godwin, Alicia S. Wellman, Aisa Sakaguchi, Shawn Ahmed
doi: https://doi.org/10.1101/326751
Matt Simon
1Department of Genetics and Molecular Biology, University of North Carolina, Chapel Hill, NC, USA
2Department of Biology and Molecular Biology, University of North Carolina, Chapel Hill, NC, USA
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Maya Spichal
1Department of Genetics and Molecular Biology, University of North Carolina, Chapel Hill, NC, USA
2Department of Biology and Molecular Biology, University of North Carolina, Chapel Hill, NC, USA
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Bree Heestand
1Department of Genetics and Molecular Biology, University of North Carolina, Chapel Hill, NC, USA
2Department of Biology and Molecular Biology, University of North Carolina, Chapel Hill, NC, USA
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Stephen Frenk
1Department of Genetics and Molecular Biology, University of North Carolina, Chapel Hill, NC, USA
2Department of Biology and Molecular Biology, University of North Carolina, Chapel Hill, NC, USA
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Ashley Hedges
2Department of Biology and Molecular Biology, University of North Carolina, Chapel Hill, NC, USA
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Malik Godwin
1Department of Genetics and Molecular Biology, University of North Carolina, Chapel Hill, NC, USA
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Alicia S. Wellman
1Department of Genetics and Molecular Biology, University of North Carolina, Chapel Hill, NC, USA
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Aisa Sakaguchi
1Department of Genetics and Molecular Biology, University of North Carolina, Chapel Hill, NC, USA
2Department of Biology and Molecular Biology, University of North Carolina, Chapel Hill, NC, USA
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Shawn Ahmed
1Department of Genetics and Molecular Biology, University of North Carolina, Chapel Hill, NC, USA
2Department of Biology and Molecular Biology, University of North Carolina, Chapel Hill, NC, USA
3Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, NC, USA
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  • For correspondence: shawn@med.unc.edu
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Abstract

Mutation of the daf-2 insulin/IGF-1 receptor activates the DAF-16/Foxo transcription factor to suppress the transgenerational sterility phenotype of prg-1/piRNA mutants that are deficient for piRNA-mediated genome silencing. As with PRG-1/piRNAs, mutations in the nuclear RNA interference gene nrde-1 compromised germ cell immortality, but deficiency for daf-2 did not suppress the transgenerational sterility of nrde-1 or nrde-4 single mutants or of prg-1; nrde-4 or prg-1; hrde-1 double mutants. NRDE-1 and NRDE-4 promote transcriptional silencing in somatic cells via the nuclear Argonaute protein NRDE-3, which was dispensable for germ cell immortality. However, daf-2 deficiency failed to promote germ cell immortality in prg-1; nrde-3 mutants. Consistently, we found that DAF-16 activity in somatic cells suppressed the transgenerational sterility of prg-1 mutants via the SID-1 dsRNA transmembrane channel that promotes systemic RNAi as well as Dicer, the dsRNA binding protein RDE-4 and the RDRP RRF-3. We conclude that DAF-16 activates a cell-non-autonomous systemic RNAi pathway that promotes small RNA-mediated genome silencing in germ cells to suppress loss of the genomic immune surveillance factor Piwi/PRG-1.

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Posted May 20, 2018.
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DAF-16/Foxo suppresses the transgenerational sterility of prg-1 piRNA mutants via a systemic small RNA pathway
Matt Simon, Maya Spichal, Bree Heestand, Stephen Frenk, Ashley Hedges, Malik Godwin, Alicia S. Wellman, Aisa Sakaguchi, Shawn Ahmed
bioRxiv 326751; doi: https://doi.org/10.1101/326751
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DAF-16/Foxo suppresses the transgenerational sterility of prg-1 piRNA mutants via a systemic small RNA pathway
Matt Simon, Maya Spichal, Bree Heestand, Stephen Frenk, Ashley Hedges, Malik Godwin, Alicia S. Wellman, Aisa Sakaguchi, Shawn Ahmed
bioRxiv 326751; doi: https://doi.org/10.1101/326751

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