DDX3 is critical for female fertility via translational control in oogenesis.

IF 6.1 2区生物学 Q1 CELL BIOLOGY Cell Death Discovery Pub Date : 2024-11-17 DOI:10.1038/s41420-024-02242-6

Shang-Yu Tsai, Chih-Hung Lin, Yu-Ting Jiang, Guo-Jen Huang, Haiwei Pi, Hsin-Yuan Hung, Woan-Yuh Tarn, Ming-Chih Lai

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Abstract

DEAD-box RNA helicase 3 (DDX3) and its homologs play a vital role in translation initiation by unwinding secondary structures of selected mRNAs. The human DDX3 gene is located on the sex chromosomes, so there are DDX3X and DDX3Y. DDX3X is ubiquitously expressed in almost all tissues and critical for embryonic development, whereas DDX3Y is only expressed in the testis and essential for male fertility. Drosophila belle (bel) is the single ortholog of DDX3, and mutations in bel cause male and female infertility. Using Drosophila bel mutants and Ddx3x conditional knockout (cKO) mice, we confirmed the pivotal role of DDX3 in female fertility and ovarian development. Drosophila bel mutants exhibited female infertility and immature egg chambers. Consistently, oocyte-specific Ddx3x knockout in mice resulted in female infertility and impaired oogenesis. We further found that immature egg chambers in Drosophila bel mutants and impaired follicular development in oocyte-specific Ddx3x cKO mice were caused by excessive apoptosis. We also identified a set of DDX3 target genes involved in oocyte meiosis and maturation and demonstrated that DDX3 is involved in their translation in human cells. Our results suggest that DDX3 is critical for female fertility via translational control in oogenesis.

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DDX3 在卵子生成过程中通过翻译控制对雌性生育能力至关重要。

DEAD-box RNA 螺旋酶 3（DDX3）及其同源物通过解开选定 mRNA 的二级结构，在翻译启动过程中发挥着重要作用。人类的 DDX3 基因位于性染色体上，因此有 DDX3X 和 DDX3Y 之分。DDX3X 在几乎所有组织中普遍表达，对胚胎发育至关重要，而 DDX3Y 只在睾丸中表达，对男性生育力至关重要。果蝇belle（bel）是DDX3的单个直向同源物，bel突变会导致雄性和雌性不育。利用果蝇bel突变体和Ddx3x条件性基因敲除（cKO）小鼠，我们证实了DDX3在雌性生育能力和卵巢发育中的关键作用。果蝇bel突变体表现出雌性不孕和卵室不成熟。同样，小鼠卵母细胞特异性 Ddx3x 基因敲除也会导致雌性不孕和卵子生成障碍。我们进一步发现，果蝇bel突变体中不成熟的卵室和卵母细胞特异性Ddx3x cKO小鼠中受损的卵泡发育是由过度的细胞凋亡造成的。我们还发现了一组参与卵母细胞减数分裂和成熟的 DDX3 靶基因，并证明 DDX3 参与了这些基因在人体细胞中的翻译。我们的研究结果表明，DDX3 在卵子发生过程中通过翻译控制对女性生育至关重要。

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

Cell Death Discovery Biochemistry, Genetics and Molecular Biology-Cell Biology

CiteScore

8.30

自引率

1.40%

发文量

468

审稿时长

9 weeks

期刊介绍： Cell Death Discovery is a multidisciplinary, international, online-only, open access journal, dedicated to publishing research at the intersection of medicine with biochemistry, pharmacology, immunology, cell biology and cell death, provided it is scientifically sound. The unrestricted access to research findings in Cell Death Discovery will foster a dynamic and highly productive dialogue between basic scientists and clinicians, as well as researchers in industry with a focus on cancer, neurobiology and inflammation research. As an official journal of the Cell Death Differentiation Association (ADMC), Cell Death Discovery will build upon the success of Cell Death & Differentiation and Cell Death & Disease in publishing important peer-reviewed original research, timely reviews and editorial commentary. Cell Death Discovery is committed to increasing the reproducibility of research. To this end, in conjunction with its sister journals Cell Death & Differentiation and Cell Death & Disease, Cell Death Discovery provides a unique forum for scientists as well as clinicians and members of the pharmaceutical and biotechnical industry. It is committed to the rapid publication of high quality original papers that relate to these subjects, together with topical, usually solicited, reviews, editorial correspondence and occasional commentaries on controversial and scientifically informative issues.