PNUTS:PP1 recruitment to Tox4 regulates chromosomal dispersal in Drosophila germline development.

IF 7.5 1区生物学 Q1 CELL BIOLOGY

Cell reports Pub Date : 2025-05-09 DOI:10.1016/j.celrep.2025.115693

Louise Duncalf, Xinru Wang, Abdulrahman A Aljabri, Amy E Campbell, Rawan Q Alharbi, Ian Donaldson, Andrew Hayes, Wolfgang Peti, Rebecca Page, Daimark Bennett

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引用次数: 0

Abstract

Ser/Thr protein phosphatase 1 (PP1) forms a large nuclear holoenzyme (with PNUTS, WDR82, and Tox4) whose emerging role is to regulate transcription. However, the role of Tox4, and its interplay with the other phosphatase subunits in this complex, is poorly understood. Here, we combine biochemical, structural, cellular, and in vivo experiments to show that, while tox4 is dispensable for viability, it is essential for fertility, having both PNUTS-dependent and -independent roles in Drosophila germline development. We also show that Tox4 requires zinc for PNUTS TFIIS N-terminal domain (TND) binding, and that it binds the TND on a surface distinct from that used by established TND-interacting transcriptional regulators. We also show that selective disruption of the PNUTS-Tox4 and the PNUTS-PP1 interaction is critical for normal gene expression and chromosomal dispersal during oogenesis. Together, these data demonstrate how interactions within the PNUTS-Tox4-PP1 phosphatase combine to tune transcriptional outputs driving developmental transitions.

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PNUTS:PP1向Tox4募集调节果蝇种系发育中的染色体分散。

丝氨酸/苏氨酸蛋白磷酸酶1 （Ser/Thr protein phosphatase 1, PP1）形成一个大的核全酶（与PNUTS、WDR82和Tox4一起），其新出现的作用是调节转录。然而，Tox4的作用及其与该复合体中其他磷酸酶亚基的相互作用尚不清楚。在这里，我们结合生化、结构、细胞和体内实验表明，虽然tox4对生存能力是必不可少的，但它对生殖能力是必不可少的，在果蝇种系发育中具有pnuts依赖性和非依赖性作用。我们还表明，Tox4需要锌才能与PNUTS TFIIS n端结构域（TND）结合，并且它在与已建立的TND相互作用转录调控因子不同的表面上结合TND。我们还发现，PNUTS-Tox4和PNUTS-PP1相互作用的选择性破坏对卵子发生过程中正常基因表达和染色体扩散至关重要。总之，这些数据证明了PNUTS-Tox4-PP1磷酸酶内部的相互作用如何结合起来调节转录输出，从而驱动发育转变。

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 reports CELL BIOLOGY-

CiteScore

13.80

自引率

1.10%

发文量

1305

审稿时长

77 days

期刊介绍： Cell Reports publishes high-quality research across the life sciences and focuses on new biological insight as its primary criterion for publication. The journal offers three primary article types: Reports, which are shorter single-point articles, research articles, which are longer and provide deeper mechanistic insights, and resources, which highlight significant technical advances or major informational datasets that contribute to biological advances. Reviews covering recent literature in emerging and active fields are also accepted. The Cell Reports Portfolio includes gold open-access journals that cover life, medical, and physical sciences, and its mission is to make cutting-edge research and methodologies available to a wide readership. The journal's professional in-house editors work closely with authors, reviewers, and the scientific advisory board, which consists of current and future leaders in their respective fields. The advisory board guides the scope, content, and quality of the journal, but editorial decisions are independently made by the in-house scientific editors of Cell Reports.