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内源性复原病毒样蛋白招募UBQLN2来应激颗粒,并塑造它们的功能生物学
Harihar M Mohan1,2, Martin G Fernandez3,4, Camellia Huang2
1Cellular and Molecular Biology Program, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Science advances
|July 18, 2025
概括
细胞蛋白质稳定异常与内源性复原病毒样蛋白质有意想不到的联系. 逆转移素像8 (RTL8) 和父性表达基因10 (PEG10) 调节UBQLN2,影响压力颗粒动态.
科学领域:
- 分子生物学分子生物学
- 基因组学就是基因组学.
- 细胞生物学 细胞生物学
背景情况:
- 人类基因组包含来自外来元素的众多序列,包括内源性复原病毒样蛋白质,其功能尚不清楚.
- UBQLN2是一种全方位蛋白酶转运因子,与神经退行性疾病有关.
研究的目的:
- 调查复原病毒样蛋白的调节作用,特别是复原转移素像8 (RTL8) 和父性表达基因10 (PEG10),对UBQLN2的功能.
- 阐明这些相互作用对细胞蛋白质稳定和压力颗粒动态的影响.
主要方法:
- 研究了UBQLN2,RTL8和PEG10之间的蛋白质-蛋白质相互作用.
- 评估了UBQLN2在各种压力条件下对应力颗粒的招募.
- 分析了改变蛋白质水平对应力颗粒分解和翻译恢复动力学的影响.
- 检查了压力颗粒的组成和PEG10的病毒样颗粒的形成.
主要成果:
- RTL8使UBQLN2能够与PEG10结合并调节它.
- 根据RTL8的存在,PEG10将UBQLN2招募到应力颗粒中.
- UBQLN2,RTL8或PEG10水平的变化会改变应力颗粒的分解和翻译恢复.
- PEG10将细胞外囊泡蛋白纳入压力颗粒,并在其中形成类似病毒的颗粒.
结论:
- 揭示了细胞蛋白质稳定路径和内源性复原病毒样蛋白之间的新鲜联系.
- 证明RTL8和PEG10是UBQLN2的关键调节剂,影响其在压力颗粒形成和分离中的作用.
- 突出了应力颗粒的结构异质性,其中PEG10在它们内部形成病毒样颗粒.
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