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雌性生殖系特异性蛋白樱花与卵巢肿瘤相关去泛素化酶相互作用,对生殖系干细胞的更新、分化及卵子发生至关重要。

Female-germline specific protein Sakura interacts with Otu and is crucial for germline stem cell renewal and differentiation and oogenesis.

作者信息

Azlan Azali, Zhu Li, Fukunaga Ryuya

出版信息

bioRxiv. 2025 Jun 4:2024.10.04.616675. doi: 10.1101/2024.10.04.616675.

Abstract

During oogenesis, self-renewal and differentiation of germline stem cells (GSCs) must be tightly regulated. The female germline serves as an excellent model for studying these regulatory mechanisms. Here, we report that a previously uncharacterized gene , which we named , is essential for oogenesis and female fertility in . Sakura is predominantly expressed in the ovaries, particularly in the germline cells, including GSCs. null mutant female flies display rudimentary ovaries with germline-less and tumorous phenotypes, fail to produce eggs, and are completely sterile. The germline-specific depletion of impairs Dpp/BMP signaling, leading to aberrant ( ) expression, resulting in faulty differentiation and loss of GSCs. is also necessary for normal levels of piwi-interacting RNAs (piRNAs) levels and for female-specific splicing of ( ), a master regulator of sex identity determination. We identified Ovarian Tumor (Otu) as a protein binding partner of Sakura and found that loss of phenocopies loss of in ovaries. Thus, we identify Sakura as a crucial factor for GSC renewal and differentiation and oogenesis, and propose that Sakura and Otu function together in these processes.

摘要

在卵子发生过程中,生殖系干细胞(GSCs)的自我更新和分化必须受到严格调控。雌性生殖系是研究这些调控机制的绝佳模型。在此,我们报告一个先前未被鉴定的基因,我们将其命名为Sakura,它对于果蝇的卵子发生和雌性生育能力至关重要。Sakura主要在卵巢中表达,特别是在包括GSCs在内的生殖系细胞中。Sakura基因敲除的雌性果蝇表现出卵巢发育不全,具有无生殖系和肿瘤样表型,无法产卵,并且完全不育。生殖系特异性敲除Sakura会损害Dpp/BMP信号通路,导致异常的bag-of-marbles(bam)表达,从而导致分化异常和GSCs丢失。Sakura对于正常水平的piwi相互作用RNA(piRNAs)水平以及性别身份决定的主要调节因子transformer(tra)的雌性特异性剪接也是必需的。我们鉴定出卵巢肿瘤(Otu)是Sakura的蛋白质结合伴侣,并发现Sakura缺失在卵巢中的表型模拟了Otu缺失的表型。因此,我们确定Sakura是GSC更新、分化和卵子发生的关键因素,并提出Sakura和Otu在这些过程中共同发挥作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d661/12233621/6a423c8aacb2/nihpp-2024.10.04.616675v4-f0001.jpg

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