A genetic framework for RNAi inheritance in Caenorhabditis elegans.

IF 6.5 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

EMBO Reports Pub Date : 2025-07-07 DOI:10.1038/s44319-025-00512-7

Jan Schreier, Lizaveta Pshanichnaya, Fridolin Kielisch, René F Ketting

{"title":"A genetic framework for RNAi inheritance in Caenorhabditis elegans.","authors":"Jan Schreier, Lizaveta Pshanichnaya, Fridolin Kielisch, René F Ketting","doi":"10.1038/s44319-025-00512-7","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":""},"PeriodicalIF":6.5000,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"EMBO Reports","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1038/s44319-025-00512-7","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}

引用次数: 0

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.

查看原文本刊更多论文

秀丽隐杆线虫RNAi遗传的遗传框架。

RNA干扰（RNAi）基因调控是由双链RNA （dsRNA）驱动的保守过程。它响应外源信号并驱动内源性基因调控。在秀丽隐杆线虫中，RNAi可以从父母遗传给后代。虽然许多因素都涉及到这一遗传过程，但我们不了解它们是如何以及何时起作用的。使用新的遗传分析，我们建立了一个层次结构之间的先前确定的遗传因素。我们发现细胞核Argonaute蛋白HRDE-1是在亲本和后代中建立RNAi所必需的，但不是遗传过程所必需的。相比之下，细胞质Argonaute蛋白WAGO-3是通过精子和卵母细胞遗传的唯一必要因子，而不影响亲本或后代的建立。我们提出了一个周期，其中核和细胞质Argonaute蛋白相互作用，产生沉默反应和细胞质因子WAGO-3，该因子在亲本和子代之间传递沉默。最后，我们暗示RNA解旋酶ZNFX-1是允许遗传WAGO-3蛋白触发后代沉默的一个因素。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

EMBO Reports 生物-生化与分子生物学

CiteScore

11.20

自引率

1.30%

发文量

267

审稿时长

1 months

期刊介绍： EMBO Reports is a scientific journal that specializes in publishing research articles in the fields of molecular biology, cell biology, and developmental biology. The journal is known for its commitment to publishing high-quality, impactful research that provides novel physiological and functional insights. These insights are expected to be supported by robust evidence, with independent lines of inquiry validating the findings. The journal's scope includes both long and short-format papers, catering to different types of research contributions. It values studies that: Communicate major findings: Articles that report significant discoveries or advancements in the understanding of biological processes at the molecular, cellular, and developmental levels. Confirm important findings: Research that validates or supports existing knowledge in the field, reinforcing the reliability of previous studies. Refute prominent claims: Studies that challenge or disprove widely accepted ideas or hypotheses in the biosciences, contributing to the correction and evolution of scientific understanding. Present null data: Papers that report negative results or findings that do not support a particular hypothesis, which are crucial for the scientific process as they help to refine or redirect research efforts. EMBO Reports is dedicated to maintaining high standards of scientific rigor and integrity, ensuring that the research it publishes contributes meaningfully to the advancement of knowledge in the life sciences. By covering a broad spectrum of topics and encouraging the publication of both positive and negative results, the journal plays a vital role in promoting a comprehensive and balanced view of scientific inquiry.