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小分子核糖核蛋白颗粒蛋白 SmD3 调控生殖干细胞的稳态和剪接体与核糖体信号之间的串扰。

Small ribonucleoprotein particle protein SmD3 governs the homeostasis of germline stem cells and the crosstalk between the spliceosome and ribosome signals in .

机构信息

Department of Gynecology, The Affiliated Hospital of Jiangsu University-Jiangsu University, Zhenjiang, China.

Reproductive Sciences Institute, Jiangsu University, Zhenjiang, China.

出版信息

FASEB J. 2019 Jul;33(7):8125-8137. doi: 10.1096/fj.201802536RR. Epub 2019 Mar 28.

Abstract

The ribonucleoprotein (RNP) spliceosome machinery triggers the precursor RNA splicing process in eukaryotes. Major spliceosome defects are implicated in male infertility; however, the underlying mechanistic links between the spliceosome and the ribosome in testes remains largely unresolved. Small ribonucleoprotein particle protein SmD3 (SmD3) is a novel germline stem cell (GSC) regulatory gene identified in our previous screen of testes. In the present study, using genetic manipulation in a model, we demonstrated that SmD3 is required for the GSC niche and controls the self-renewal and differentiation of GSCs in the testis. Using assays in Schneider 2 cells, we showed that SmD3 also regulates the homeostasis of proliferation and apoptosis in . Furthermore, using liquid chromatography-tandem mass spectrometry methods, SmD3 was identified as binding with ribosomal protein (Rp)L18, which is a key regulator of the large subunit in the ribosome. Moreover, SmD3 was observed to regulate spliceosome and ribosome subunit expression levels and controlled spliceosome and ribosome function RpL18. Significantly, our findings revealed the genetic causes and molecular mechanisms underlying the stem cell niche and the crosstalk between the spliceosome and the ribosome.-Yu, J., Luan, X., Yan, Y., Qiao, C., Liu, Y., Zhao, D., Xie, B., Zheng, Q., Wang, M., Chen, W., Shen, C., He, Z., Hu, X., Huang, X., Li, H., Chen, B., Zheng, B., Chen, X., Fang, J. Small ribonucleoprotein particle protein SmD3 governs the homeostasis of germline stem cells and the crosstalk between the spliceosome and ribosome signals in .

摘要

核糖核蛋白(RNP)剪接体机制在真核生物中触发前体 RNA 的剪接过程。主要剪接体缺陷与男性不育有关;然而,睾丸中剪接体和核糖体之间的潜在机制联系在很大程度上仍未得到解决。小核糖核蛋白颗粒蛋白 SmD3(SmD3)是我们之前在 睾丸筛选中鉴定的一种新的生殖细胞干细胞(GSC)调节基因。在本研究中,我们使用模型中的遗传操作证明 SmD3 是 GSC 龛所必需的,并控制睾丸中 GSC 的自我更新和分化。在 Schneider 2 细胞中使用 测定法,我们表明 SmD3 还调节增殖和凋亡的动态平衡。此外,使用液相色谱-串联质谱方法,SmD3 被鉴定为与核糖体蛋白(Rp)L18 结合,L18 是核糖体大亚基的关键调节剂。此外,观察到 SmD3 调节剪接体和核糖体亚基表达水平,并控制剪接体和核糖体功能 RpL18。重要的是,我们的发现揭示了干细胞龛的遗传原因和分子机制以及剪接体和核糖体之间的串扰。-于,J.,Luan,X.,Yan,Y.,Qiao,C.,Liu,Y.,Zhao,D.,Xie,B.,Zheng,Q.,Wang,M.,Chen,W.,Shen,C.,He,Z.,Hu,X.,Huang,X.,Li,H.,Chen,B.,Zheng,B.,Chen,X.,Fang,J. 小核糖核蛋白颗粒蛋白 SmD3 调节生殖细胞干细胞的动态平衡以及剪接体和核糖体信号之间的串扰。

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