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核孔蛋白107通过阻止初级微小核糖核酸427过早的核输出,促进母源-合子转变。

Nup107 contributes to the maternal-to-zygotic transition by preventing the premature nuclear export of pri-miR427.

作者信息

Kostiuk Valentyna, Kabir Rakib, Levangie Kaitlin, Empke Stefany, Morgan Kimberly, Owens Nick D L, Lusk C Patrick, Khokha Mustafa K

机构信息

Pediatric Genomics Discovery Program, Departments of Pediatrics and Genetics, Yale School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA.

Department of Cell Biology, Yale School of Medicine, 295 Congress Avenue, New Haven, CT 06520, USA.

出版信息

Development. 2025 Jan 15;152(2). doi: 10.1242/dev.202865. Epub 2025 Feb 4.

Abstract

Emerging evidence suggests that the nuclear pore complex can have unique compositions and distinct nucleoporin functions in different cells. Here, we show that Nup107, a key component of the NPC scaffold, varies in expression over development: it is expressed at higher levels in the blastula compared to the gastrula, suggesting a crucial role before gastrulation in Xenopus. We find that depletion of Nup107 affects the differentiation of the early germ layers leading to an expansion of the ectoderm at the expense of endoderm and mesoderm. By analyzing an RNA-sequencing time course, we observed that depletion of Nup107 affects the maternal-zygotic transition by delaying the degradation of maternal transcripts that occurs as zygotic transcription begins. The transcripts are enriched in recognition sites for miR427, a conserved microRNA that destabilizes maternal transcripts including REST, which encodes a Kruppel-type zinc-finger transcription factor that we demonstrate is crucial for ectodermal cell fates. Mechanistically, we show that Nup107 is required to prevent the premature export of pri-miR427 transcript before processing. Nup107 depletion leads to the reduced production of mature miR427 and maternal transcript stabilization. We conclude that high levels of Nup107 in the early embryo are crucial for the nuclear retention and subsequent processing of pri-miR427 transcripts that is required for timely maternal RNA clearance to enable gastrulation.

摘要

新出现的证据表明,核孔复合体在不同细胞中可能具有独特的组成和不同的核孔蛋白功能。在这里,我们表明Nup107是核孔复合体支架的关键组成部分,其表达在发育过程中有所变化:与原肠胚相比,它在囊胚中的表达水平更高,这表明其在非洲爪蟾原肠胚形成之前发挥着关键作用。我们发现,Nup107的缺失会影响早期胚层的分化,导致外胚层扩张,以内胚层和中胚层为代价。通过分析RNA测序时间进程,我们观察到Nup107的缺失会影响母源-合子转变,延迟母源转录本在合子转录开始时的降解。这些转录本富含miR427的识别位点,miR427是一种保守的微小RNA,可使包括REST在内的母源转录本不稳定,我们证明REST编码一种Kruppel型锌指转录因子,对表皮细胞命运至关重要。从机制上讲,我们表明Nup107是防止pri-miR427转录本在加工前过早输出所必需的。Nup107的缺失导致成熟miR427的产生减少和母源转录本的稳定。我们得出结论,早期胚胎中高水平的Nup107对于pri-miR427转录本的核滞留和后续加工至关重要,而这是及时清除母源RNA以实现原肠胚形成所必需的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3650/11829755/6d767cf09408/develop-152-202865-g1.jpg

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