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DDX3通过在卵子发生过程中的翻译控制对雌性生育至关重要。

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

作者信息

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

机构信息

Department of Biomedical Sciences, Chang Gung University, Taoyuan, Taiwan.

Graduate Institute of Biomedical Sciences, Chang Gung University, Taoyuan, Taiwan.

出版信息

Cell Death Discov. 2024 Nov 17;10(1):472. doi: 10.1038/s41420-024-02242-6.

DOI:10.1038/s41420-024-02242-6
PMID:39551844
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11570671/
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.

摘要

DEAD盒RNA解旋酶3（DDX3）及其同源物通过解开特定mRNA的二级结构在翻译起始中发挥重要作用。人类DDX3基因位于性染色体上，因此存在DDX3X和DDX3Y。DDX3X在几乎所有组织中普遍表达，对胚胎发育至关重要，而DDX3Y仅在睾丸中表达，对男性生育至关重要。果蝇的belle（bel）是DDX3的单一直系同源物，bel突变会导致雄性和雌性不育。利用果蝇bel突变体和Ddx3x条件性敲除（cKO）小鼠，我们证实了DDX3在雌性生育和卵巢发育中的关键作用。果蝇bel突变体表现出雌性不育和未成熟的卵室。同样，小鼠卵母细胞特异性Ddx3x敲除导致雌性不育和卵子发生受损。我们进一步发现，果蝇bel突变体中未成熟的卵室以及卵母细胞特异性Ddx3x cKO小鼠中卵泡发育受损是由过度凋亡引起的。我们还鉴定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在人类细胞中参与它们的翻译。我们的结果表明，DDX3通过卵子发生中的翻译控制对雌性生育至关重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/486f/11570671/21140f6882e5/41420_2024_2242_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/486f/11570671/505734ee3510/41420_2024_2242_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/486f/11570671/407b87c512f0/41420_2024_2242_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/486f/11570671/c6e5da7ba8f2/41420_2024_2242_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/486f/11570671/215bd4cc6c15/41420_2024_2242_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/486f/11570671/a567141f6874/41420_2024_2242_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/486f/11570671/40fb15bd5772/41420_2024_2242_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/486f/11570671/503e0156bf14/41420_2024_2242_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/486f/11570671/21140f6882e5/41420_2024_2242_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/486f/11570671/505734ee3510/41420_2024_2242_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/486f/11570671/407b87c512f0/41420_2024_2242_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/486f/11570671/c6e5da7ba8f2/41420_2024_2242_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/486f/11570671/215bd4cc6c15/41420_2024_2242_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/486f/11570671/a567141f6874/41420_2024_2242_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/486f/11570671/40fb15bd5772/41420_2024_2242_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/486f/11570671/503e0156bf14/41420_2024_2242_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/486f/11570671/21140f6882e5/41420_2024_2242_Fig8_HTML.jpg

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