title: The C. elegans CSR-1 argonaute pathway counteracts epigenetic silencing to promote germline gene expression.
abstract: Organisms can develop adaptive sequence-specific immunity by reexpressing pathogen-specific small RNAs that guide gene silencing. For example, the C. elegans PIWI-Argonaute/piwi-interacting RNA (piRNA) pathway recruits RNA-dependent RNA polymerase (RdRP) to foreign sequences to amplify a transgenerational small-RNA-induced epigenetic silencing signal (termed RNAe). Here, we provide evidence that, in addition to an adaptive memory of silenced sequences, C. elegans can also develop an opposing adaptive memory of expressed/self-mRNAs. We refer to this mechanism, which can prevent or reverse RNAe, as RNA-induced epigenetic gene activation (RNAa). We show that CSR-1, which engages RdRP-amplified small RNAs complementary to germline-expressed mRNAs, is required for RNAa. We show that a transgene with RNAa activity also exhibits accumulation of cognate CSR-1 small RNAs. Our findings suggest that C. elegans adaptively acquires and maintains a transgenerational CSR-1 memory that recognizes and protects self-mRNAs, allowing piRNAs to recognize foreign sequences innately, without the need for prior exposure
authors.forename: Meetu
authors.initials: M
authors.lastname: Seth
authors.forename: Masaki
authors.initials: M
authors.lastname: Shirayama
authors.forename: Weifeng
authors.initials: W
authors.lastname: Gu
authors.forename: Takao
authors.initials: T
authors.lastname: Ishidate
authors.forename: Darryl
authors.initials: D
authors.lastname: Conte
authors.forename: Craig C
authors.initials: CC
authors.lastname: Mello
mesh_terms: D000818:Animals; D060565:Argonaute Proteins / Q000235:genetics / Q000378:metabolism; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D044127:Epigenesis, Genetic; D020868:Gene Silencing; D005854:Germ Cells / Q000378:metabolism*; D018510:RNA, Helminth / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism*; D012324:RNA-Dependent RNA Polymerase / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D060565:Argonaute Proteins; C544459:CSR-1 protein, C elegans; D029742:Caenorhabditis elegans Proteins; C530363:PRG-1 protein, C elegans; D018510:RNA, Helminth; D034741:RNA, Small Interfering; D012324:RNA-Dependent RNA Polymerase