ADR-2 regulates fertility and oocyte fate in Caenorhabditis elegans.

IF 3.3 3区生物学 Q2 GENETICS & HEREDITY

Genetics Pub Date : 2024-10-07 DOI:10.1093/genetics/iyae114

Emily A Erdmann, Melanie Forbes, Margaret Becker, Sarina Perez, Heather A Hundley

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引用次数: 0

Abstract

RNA-binding proteins (RBPs) play essential roles in coordinating germline gene expression and development in all organisms. Here, we report that loss of ADR-2, a member of the adenosine deaminase acting on RNA family of RBPs and the sole adenosine-to-inosine RNA-editing enzyme in Caenorhabditis elegans, can improve fertility in multiple genetic backgrounds. First, we show that loss of RNA editing by ADR-2 restores normal embryo production to subfertile animals that transgenically express a vitellogenin (yolk protein) fusion to green fluorescent protein. Using this phenotype, a high-throughput screen was designed to identify RBPs that when depleted yield synthetic phenotypes with loss of adr-2. The screen uncovered a genetic interaction between ADR-2 and SQD-1, a member of the heterogeneous nuclear ribonucleoprotein family of RBPs. Microscopy, reproductive assays, and high-throughput sequencing reveal that sqd-1 is essential for the onset of oogenesis and oogenic gene expression in young adult animals and that loss of adr-2 can counteract the effects of loss of sqd-1 on gene expression and rescue the switch from spermatogenesis to oogenesis. Together, these data demonstrate that ADR-2 can contribute to the suppression of fertility and suggest novel roles for both RNA editing-dependent and RNA editing-independent mechanisms in regulating embryogenesis.

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ADR-2调节秀丽隐杆线虫的生育能力和卵母细胞命运

RNA 结合蛋白在协调所有生物的生殖系基因表达和发育过程中发挥着至关重要的作用。在这里，我们报告了ADR-2（ADR-2是RNA结合蛋白腺苷脱氨酶（ADAR）家族中的一个成员，也是优雅小鼠中唯一的腺苷-肌苷RNA编辑酶）的缺失可以改善多种遗传背景下的生育能力。首先，我们发现，转基因表达与绿色荧光蛋白融合的卵黄素（卵黄蛋白）的亚肥育动物失去 ADR-2 的 RNA 编辑功能后，可恢复正常的胚胎生产。利用这种表型，我们设计了一个高通量筛选，以确定 RNA 结合蛋白，当这些蛋白被耗尽时，adr-2 的缺失会产生合成表型。筛选发现了 ADR-2 和 SQD-1 之间的遗传相互作用，SQD-1 是 RNA 结合蛋白异源核核糖核蛋白（hnRNP）家族的成员。显微镜、生殖测定和高通量测序显示，sqd-1 对幼年成年动物卵子发生的开始和卵子发生基因的表达至关重要，而 ADR-2 的缺失可以抵消 sqd-1 缺失对基因表达的影响，并挽救从精子发生到卵子发生的转换。这些数据共同表明，ADR-2 可抑制生育能力，并提示依赖于 RNA 编辑和独立于 RNA 编辑的机制在调节胚胎发生中的新作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Genetics GENETICS & HEREDITY-

CiteScore

6.90

自引率

6.10%

发文量

177

审稿时长

1.5 months

期刊介绍： GENETICS is published by the Genetics Society of America, a scholarly society that seeks to deepen our understanding of the living world by advancing our understanding of genetics. Since 1916, GENETICS has published high-quality, original research presenting novel findings bearing on genetics and genomics. The journal publishes empirical studies of organisms ranging from microbes to humans, as well as theoretical work. While it has an illustrious history, GENETICS has changed along with the communities it serves: it is not your mentor''s journal. The editors make decisions quickly – in around 30 days – without sacrificing the excellence and scholarship for which the journal has long been known. GENETICS is a peer reviewed, peer-edited journal, with an international reach and increasing visibility and impact. All editorial decisions are made through collaboration of at least two editors who are practicing scientists. GENETICS is constantly innovating: expanded types of content include Reviews, Commentary (current issues of interest to geneticists), Perspectives (historical), Primers (to introduce primary literature into the classroom), Toolbox Reviews, plus YeastBook, FlyBook, and WormBook (coming spring 2016). For particularly time-sensitive results, we publish Communications. As part of our mission to serve our communities, we''ve published thematic collections, including Genomic Selection, Multiparental Populations, Mouse Collaborative Cross, and the Genetics of Sex.