piRNAs can trigger a multigenerational epigenetic memory in the germline of C. elegans.
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.
Wellcome Trust Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.
Alyson
A
Ashe
Alexandra
A
Sapetschnig
Eva-Maria
EM
Weick
Jacinth
J
Mitchell
Marloes P
MP
Bagijn
Amy C
AC
Cording
Anna-Lisa
AL
Doebley
Leonard D
LD
Goldstein
Nicolas J
NJ
Lehrbach
Jérémie
J
Le Pen
Greta
G
Pintacuda
Aisa
A
Sakaguchi
Peter
P
Sarkies
Shawn
S
Ahmed
Eric A
EA
Miska
D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000378:metabolism; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D057890:Epigenomics; D005260:Female; D005854:Germ Cells / Q000378:metabolism; D008297:Male; D034622:RNA Interference; D018510:RNA, Helminth / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism*; D019076:Transgenes
D018510:RNA, Helminth; D034741:RNA, Small Interfering