{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Schreier J"],"funding":["Deutsche Forschungsgemeinschaft (DFG)","NIH HHS"],"pagination":["4072-4099"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12373942"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["26(16)"],"pubmed_abstract":["Gene regulation by RNA interference (RNAi) is a conserved process driven by double-stranded RNA (dsRNA). It responds to exogenous cues and drives endogenous gene regulation. In Caenorhabditis elegans, RNAi can be inherited from parents to offspring. While a number of factors have been implicated in this inheritance process, we do not understand how and when they function. Using a new inheritance assay, we establish a hierarchy amongst previously identified inheritance factors. We show that the nuclear Argonaute protein HRDE-1 is required for RNAi establishment in parents and offspring, but not for the inheritance process. In contrast, the cytoplasmic Argonaute protein WAGO-3 is the only factor essential for inheritance, via sperm and oocyte, while not affecting establishment in either parent or offspring. We propose a cycle in which nuclear and cytoplasmic Argonaute proteins interact to generate both a silencing response and a cytoplasmic factor that transmits the silencing between parent and offspring, WAGO-3. Finally, we implicate the RNA helicase ZNFX-1 as a factor that allows the inherited WAGO-3 protein to trigger silencing in the offspring."],"journal":["EMBO reports"],"pubmed_title":["A genetic framework for RNAi inheritance in Caenorhabditis elegans."],"pmcid":["PMC12373942"],"funding_grant_id":["ID 252386272","P40 OD010440"],"pubmed_authors":["Schreier J","Ketting RF","Kielisch F","Pshanichnaya L"],"additional_accession":[]},"is_claimable":false,"name":"A genetic framework for RNAi inheritance in Caenorhabditis elegans.","description":"Gene regulation by RNA interference (RNAi) is a conserved process driven by double-stranded RNA (dsRNA). It responds to exogenous cues and drives endogenous gene regulation. In Caenorhabditis elegans, RNAi can be inherited from parents to offspring. While a number of factors have been implicated in this inheritance process, we do not understand how and when they function. Using a new inheritance assay, we establish a hierarchy amongst previously identified inheritance factors. We show that the nuclear Argonaute protein HRDE-1 is required for RNAi establishment in parents and offspring, but not for the inheritance process. In contrast, the cytoplasmic Argonaute protein WAGO-3 is the only factor essential for inheritance, via sperm and oocyte, while not affecting establishment in either parent or offspring. We propose a cycle in which nuclear and cytoplasmic Argonaute proteins interact to generate both a silencing response and a cytoplasmic factor that transmits the silencing between parent and offspring, WAGO-3. Finally, we implicate the RNA helicase ZNFX-1 as a factor that allows the inherited WAGO-3 protein to trigger silencing in the offspring.","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Aug","modification":"2026-07-02T03:14:30.902Z","creation":"2026-07-02T03:11:52.717Z"},"accession":"S-EPMC12373942","cross_references":{"pubmed":["40624357"],"doi":["10.1038/s44319-025-00512-7"]}}