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piRNAs can trigger a multigenerational epigenetic memory in the germline of C. elegans |
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| Authors: | Ashe Alyson Sapetschnig Alexandra Weick Eva-Maria Mitchell Jacinth Bagijn Marloes P Cording Amy C Doebley Anna-Lisa Goldstein Leonard D Lehrbach Nicolas J Le Pen Jérémie Pintacuda Greta Sakaguchi Aisa Sarkies Peter Ahmed Shawn Miska Eric A |
| Institution: | 1 Wellcome Trust Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK 2 Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK 3 Department of Genetics, University of North Carolina, Chapel Hill, NC 27514 4 Department of Biology, University of North Carolina, Chapel Hill, NC 27514 5 Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, NC 27514 6 Scuola Normale Superiore, Piazza dei Cavalieri, 7, 56126 Pisa, Italy |
| Abstract: | Transgenerational effects have wide-ranging implications for human health, biological adaptation, and evolution; however, their mechanisms and biology remain poorly understood. Here, we demonstrate that a germline nuclear small RNA/chromatin pathway can maintain stable inheritance for many generations when triggered by a piRNA-dependent foreign RNA response in C. elegans. Using forward genetic screens and candidate approaches, we find that a core set of nuclear RNAi and chromatin factors is required for multigenerational inheritance of environmental RNAi and piRNA silencing. These include a germline-specific nuclear Argonaute HRDE1/WAGO-9, a HP1 ortholog HPL-2, and two putative histone methyltransferases, SET-25 and SET-32. piRNAs can trigger highly stable long-term silencing lasting at least 20 generations. Once established, this long-term memory becomes independent of the piRNA trigger but remains dependent on the nuclear RNAi/chromatin pathway. Our data present a multigenerational epigenetic inheritance mechanism induced by piRNAs. |
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