Function, targets, and evolution of Caenorhabditis elegans piRNAs.
Piwi-interacting RNAs (piRNAs) are small RNAs required to maintain germline integrity and fertility, but their mechanism of action is poorly understood. Here we demonstrate that Caenorhabditis elegans piRNAs silence transcripts in trans through imperfectly complementary sites. Target silencing is independent of Piwi endonuclease activity or "slicing." Instead, piRNAs initiate a localized secondary endogenous small interfering RNA (endo-siRNA) response. Endogenous protein-coding gene and transposon transcripts exhibit Piwi-dependent endo-siRNAs at sites complementary to piRNAs and are derepressed in Piwi mutants. Genomic loci of piRNA biogenesis are depleted of protein-coding genes and tend to overlap the start and end of transposons in sense and antisense, respectively. Our data suggest that nematode piRNA clusters are evolving to generate piRNAs against active mobile elements. Thus, piRNAs provide heritable, sequence-specific triggers for RNA interference in C. elegans.
Gurdon Institute and Department of Biochemistry, University of Cambridge, The Henry Wellcome Building of Cancer and Developmental Biology, Tennis Court Rd, Cambridge CB2 1QN, UK.
Marloes P
MP
Bagijn
Gurdon Institute and Department of Biochemistry, University of Cambridge, The Henry Wellcome Building of Cancer and Developmental Biology, Tennis Court Rd, Cambridge CB2 1QN, UK.
Leonard D
LD
Goldstein
Gurdon Institute and Department of Biochemistry, University of Cambridge, The Henry Wellcome Building of Cancer and Developmental Biology, Tennis Court Rd, Cambridge CB2 1QN, UK.
Alexandra
A
Sapetschnig
Gurdon Institute and Department of Biochemistry, University of Cambridge, The Henry Wellcome Building of Cancer and Developmental Biology, Tennis Court Rd, Cambridge CB2 1QN, UK.
Eva-Maria
EM
Weick
Laval University Cancer Research Centre, Hôtel-Dieu de Québec (CHUQ), Quebec City, Québec G1R 2J6, Canada.
Samir
S
Bouasker
Gurdon Institute and Department of Biochemistry, University of Cambridge, The Henry Wellcome Building of Cancer and Developmental Biology, Tennis Court Rd, Cambridge CB2 1QN, UK.
Nicolas J
NJ
Lehrbach
Laval University Cancer Research Centre, Hôtel-Dieu de Québec (CHUQ), Quebec City, Québec G1R 2J6, Canada.
Martin J
MJ
Simard
Gurdon Institute and Department of Biochemistry, University of Cambridge, The Henry Wellcome Building of Cancer and Developmental Biology, Tennis Court Rd, Cambridge CB2 1QN, UK.
Eric A
EA
Miska
D000818:Animals; D060565:Argonaute Proteins / Q000235:genetics; D017173:Caenorhabditis elegans / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics; D019143:Evolution, Molecular; D009154:Mutation; D034622:RNA Interference; D012330:RNA, Double-Stranded / Q000096:biosynthesis / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
D060565:Argonaute Proteins; D029742:Caenorhabditis elegans Proteins; C530363:PRG-1 protein, C elegans; C530626:PRG-2 protein, C elegans; D012330:RNA, Double-Stranded; D034741:RNA, Small Interfering