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核 GYF 蛋白 CD2BP2/U5-52K 是 T 细胞稳态所必需的。

The nuclear GYF protein CD2BP2/U5-52K is required for T cell homeostasis.

机构信息

Department of Chemistry and Biochemistry, Protein Biochemistry, Freie Universität Berlin, Berlin, Germany.

Department of Molecular Immunology, Ruhr-University Bochum, Bochum, Germany.

出版信息

Front Immunol. 2024 Sep 6;15:1415839. doi: 10.3389/fimmu.2024.1415839. eCollection 2024.

DOI:10.3389/fimmu.2024.1415839
PMID:39308865
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11412891/
Abstract

The question whether interference with the ubiquitous splicing machinery can lead to cell-type specific perturbation of cellular function is addressed here by T cell specific ablation of the general U5 snRNP assembly factor CD2BP2/U5-52K. This protein defines the family of nuclear GYF domain containing proteins that are ubiquitously expressed in eukaryotes with essential functions ascribed to early embryogenesis and organ function. Abrogating CD2BP2/U5-52K in T cells, allows us to delineate the consequences of splicing machinery interferences for T cell development and function. Increased T cell lymphopenia and T cell death are observed upon depletion of CD2BP2/U5-52K. A substantial increase in exon skipping coincides with the observed defect in the proliferation/differentiation balance in the absence of CD2BP2/U5-52K. Prominently, skipping of exon 7 in Mdm4 is observed, coinciding with upregulation of pro-apoptotic gene expression profiles upon CD2BP2/U5-52K depletion. Furthermore, we observe enhanced sensitivity of naïve T cells compared to memory T cells to changes in CD2BP2/U5-52K levels, indicating that depletion of this general splicing factor leads to modulation of T cell homeostasis. Given the recent structural characterization of the U5 snRNP and the crosslinking mass spectrometry data given here, design of inhibitors of the U5 snRNP conceivably offers new ways to manipulate T cell function in settings of disease.

摘要

这里通过 T 细胞特异性敲除通用 U5 snRNP 组装因子 CD2BP2/U5-52K 来解决干扰普遍存在的剪接机制是否会导致细胞类型特异性细胞功能紊乱的问题。该蛋白定义了核 GYF 结构域蛋白家族，该家族在真核生物中广泛表达，具有早期胚胎发生和器官功能的重要功能。在 T 细胞中敲除 CD2BP2/U5-52K，使我们能够描绘出剪接机制干扰对 T 细胞发育和功能的影响。在耗尽 CD2BP2/U5-52K 时，观察到 T 细胞淋巴细胞减少和 T 细胞死亡增加。在不存在 CD2BP2/U5-52K 的情况下，观察到外显子跳跃显著增加，同时观察到增殖/分化平衡的缺陷。突出的是，在 Mdm4 中观察到外显子 7 的跳跃，与 CD2BP2/U5-52K 耗尽时促凋亡基因表达谱的上调相吻合。此外，我们观察到与记忆 T 细胞相比，幼稚 T 细胞对 CD2BP2/U5-52K 水平变化的敏感性增强，表明这种通用剪接因子的耗竭导致 T 细胞稳态的调节。鉴于最近对 U5 snRNP 的结构特征描述和这里给出的交联质谱数据，可以设想设计 U5 snRNP 的抑制剂为在疾病情况下操纵 T 细胞功能提供新方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3776/11412891/051158de2b51/fimmu-15-1415839-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3776/11412891/2f2060cb2048/fimmu-15-1415839-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3776/11412891/6e272fa22241/fimmu-15-1415839-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3776/11412891/b88ead48bb79/fimmu-15-1415839-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3776/11412891/21da9117b98c/fimmu-15-1415839-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3776/11412891/a932b532cafd/fimmu-15-1415839-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3776/11412891/bc4bd6d7e7b5/fimmu-15-1415839-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3776/11412891/051158de2b51/fimmu-15-1415839-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3776/11412891/2f2060cb2048/fimmu-15-1415839-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3776/11412891/6e272fa22241/fimmu-15-1415839-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3776/11412891/b88ead48bb79/fimmu-15-1415839-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3776/11412891/21da9117b98c/fimmu-15-1415839-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3776/11412891/a932b532cafd/fimmu-15-1415839-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3776/11412891/bc4bd6d7e7b5/fimmu-15-1415839-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3776/11412891/051158de2b51/fimmu-15-1415839-g007.jpg

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2
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Nat Struct Mol Biol. 2024 May;31(5):752-756. doi: 10.1038/s41594-024-01250-5. Epub 2024 Mar 11.
3
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邻近蛋白质组学揭示USP44在神经母细胞瘤细胞中与BRCA2形成复合物，且是预防染色体断裂所必需的。
Biomedicines. 2024 Dec 20;12(12):2901. doi: 10.3390/biomedicines12122901.
Nat Struct Mol Biol. 2024 May;31(5):747-751. doi: 10.1038/s41594-024-01243-4. Epub 2024 Mar 11.
4
Deletion of ARGLU1 causes global defects in alternative splicing in vivo and mouse cortical malformations primarily via apoptosis.ARGLU1 的缺失导致体内选择性剪接的全局缺陷和小鼠皮质畸形，主要通过细胞凋亡。
Cell Death Dis. 2023 Aug 23;14(8):543. doi: 10.1038/s41419-023-06071-w.
5
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Nucleic Acids Res. 2022 Mar 21;50(5):2938-2958. doi: 10.1093/nar/gkac087.
6
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7
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