title: A Tunable Mechanism Determines the Duration of the Transgenerational Small RNA Inheritance in C. elegans.
abstract: In C. elegans, small RNAs enable transmission of epigenetic responses across multiple generations. While RNAi inheritance mechanisms that enable "memorization" of ancestral responses are being elucidated, the mechanisms that determine the duration of inherited silencing and the ability to forget the inherited epigenetic effects are not known. We now show that exposure to dsRNA activates a feedback loop whereby gene-specific RNAi responses dictate the transgenerational duration of RNAi responses mounted against unrelated genes, elicited separately in previous generations. RNA-sequencing analysis reveals that, aside from silencing of genes with complementary sequences, dsRNA-induced RNAi affects the production of heritable endogenous small RNAs, which regulate the expression of RNAi factors. Manipulating genes in this feedback pathway changes the duration of heritable silencing. Such active control of transgenerational effects could be adaptive, since ancestral responses would be detrimental if the environments of the progeny and the ancestors were different.
authors.affiliation: Department of Neurobiology, Wise Faculty of Life Sciences and Sagol School, Tel Aviv University, Tel Aviv 6997801, Israel. Electronic address: leah.houri@gmail.com.
authors.forename: Leah
authors.initials: L
authors.lastname: Houri-Ze'evi
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Yael
authors.initials: Y
authors.lastname: Korem
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Hila
authors.initials: H
authors.lastname: Sheftel
authors.affiliation: Department of Neurobiology, Wise Faculty of Life Sciences and Sagol School, Tel Aviv University, Tel Aviv 6997801, Israel.
authors.forename: Lior
authors.initials: L
authors.lastname: Faigenbloom
authors.affiliation: Department of Neurobiology, Wise Faculty of Life Sciences and Sagol School, Tel Aviv University, Tel Aviv 6997801, Israel.
authors.forename: Itai Antoine
authors.initials: IA
authors.lastname: Toker
authors.affiliation: Department of Neurobiology, Wise Faculty of Life Sciences and Sagol School, Tel Aviv University, Tel Aviv 6997801, Israel.
authors.forename: Yael
authors.initials: Y
authors.lastname: Dagan
authors.affiliation: Department of Neurobiology, Wise Faculty of Life Sciences and Sagol School, Tel Aviv University, Tel Aviv 6997801, Israel.
authors.forename: Lama
authors.initials: L
authors.lastname: Awad
authors.affiliation: Department of Neurobiology, Wise Faculty of Life Sciences and Sagol School, Tel Aviv University, Tel Aviv 6997801, Israel.
authors.forename: Luba
authors.initials: L
authors.lastname: Degani
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Uri
authors.initials: U
authors.lastname: Alon
authors.affiliation: Department of Neurobiology, Wise Faculty of Life Sciences and Sagol School, Tel Aviv University, Tel Aviv 6997801, Israel. Electronic address: odedrechavi@gmail.com.
authors.forename: Oded
authors.initials: O
authors.lastname: Rechavi
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D044127:Epigenesis, Genetic; D005246:Feedback; D034622:RNA Interference; D012330:RNA, Double-Stranded / Q000378:metabolism; D018510:RNA, Helminth / Q000235:genetics*; D034741:RNA, Small Interfering / Q000378:metabolism; D058727:RNA, Small Untranslated / Q000235:genetics*
chemical_list: D012330:RNA, Double-Stranded; D018510:RNA, Helminth; D034741:RNA, Small Interfering; D058727:RNA, Small Untranslated