MIB2 通过调节染色质构型在卵母细胞减数分裂中发挥作用。

IF 6.1 2区生物学 Q1 BIOCHEMICAL RESEARCH METHODS

Molecular & Cellular Proteomics Pub Date : 2024-08-01 Epub Date: 2024-07-15 DOI:10.1016/j.mcpro.2024.100813

Yifei Jin, Guangyi Sun, Jiashuo Li, Qing Cheng, Hongzheng Sun, Longsen Han, Xuejiang Guo, Shuai Zhu, Qiang Wang

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引用次数: 0

摘要

染色质构型是 GV（生殖囊）期卵母细胞质量的主要指标。然而，染色质构型从NSN（非包围核仁）向SN（包围核仁）转变的内在机制仍不清楚。在本研究中，通过定量蛋白质组分析，我们发现在SN卵母细胞中，MIB2（MIB E3泛素蛋白连接酶2）蛋白的表达量有所增加。在SN卵母细胞中特异性消耗MIB2不仅会导致减数分裂装置的严重破坏和非整倍体的高发生率，还会对减数分裂成熟和早期胚胎发育产生不利影响。值得注意的是，MIB2 在 NSN 卵母细胞中的过表达促进了染色质构型的转变。同时，我们观察到，在 NSN 卵母细胞中强制表达 MIB2 能显著缓解纺锤体/染色体紊乱和非整倍体现象。总之，我们的研究结果表明，MIB2调控的染色质构型转换对卵母细胞获得发育能力至关重要。

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MIB2 Functions in Oocyte Meiosis by Modulating Chromatin Configuration.

Chromatin configuration serves as a principal indicator of GV (germinal vesicle)-stage oocyte quality. However, the underlying mechanisms governing the chromatin configuration transition from NSN (non-surrounded nucleolus) to SN (surrounded nucleolus) remain unclear. In this study, by conducting a quantitative proteomic analysis, we identified an increased expression of the MIB2 (MIB E3 ubiquitin protein ligase 2) protein in SN oocytes. Specific depletion of MIB2 in SN oocytes not only leads to severe disruption of the meiotic apparatus and a higher incidence of aneuploidy but also adversely affects meiotic maturation and early embryo development. Notably, overexpression of MIB2 in NSN oocytes facilitates the chromatin configuration transition. Meantime, we observed that forced expression of MIB2 in NSN oocytes significantly mitigates spindle/chromosome disorganization and aneuploidy. In summary, our results suggest that chromatin configuration transition regulated by MIB2 is crucial for oocytes to acquire developmental competence.

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来源期刊

Molecular & Cellular Proteomics 生物-生化研究方法

CiteScore

11.50

自引率

4.30%

发文量

131

审稿时长

84 days

期刊介绍： The mission of MCP is to foster the development and applications of proteomics in both basic and translational research. MCP will publish manuscripts that report significant new biological or clinical discoveries underpinned by proteomic observations across all kingdoms of life. Manuscripts must define the biological roles played by the proteins investigated or their mechanisms of action. The journal also emphasizes articles that describe innovative new computational methods and technological advancements that will enable future discoveries. Manuscripts describing such approaches do not have to include a solution to a biological problem, but must demonstrate that the technology works as described, is reproducible and is appropriate to uncover yet unknown protein/proteome function or properties using relevant model systems or publicly available data. Scope: -Fundamental studies in biology, including integrative "omics" studies, that provide mechanistic insights -Novel experimental and computational technologies -Proteogenomic data integration and analysis that enable greater understanding of physiology and disease processes -Pathway and network analyses of signaling that focus on the roles of post-translational modifications -Studies of proteome dynamics and quality controls, and their roles in disease -Studies of evolutionary processes effecting proteome dynamics, quality and regulation -Chemical proteomics, including mechanisms of drug action -Proteomics of the immune system and antigen presentation/recognition -Microbiome proteomics, host-microbe and host-pathogen interactions, and their roles in health and disease -Clinical and translational studies of human diseases -Metabolomics to understand functional connections between genes, proteins and phenotypes