通过链域介导的核凝结,CELF2促进了tau exon 10的纳入
Xin Li1,2, Ishana Syed1, Zhao Zhang2
1Barshop Institute for Longevity and Aging Studies, Department of Cell Systems and Anatomy, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
bioRxiv : the preprint server for biology
|November 18, 2024
概括
CELF2蛋白通过与其他因素形成凝结物来调节Tau的替代拼接,从而影响神经退行性疾病的风险. 它的内在无序区域 (IDR) 是这个功能的关键.
科学领域:
- 分子生物学分子生物学
- 神经科学是一个神经科学.
- 遗传学 遗传学 是一个
背景情况:
- 替代拼接产生蛋白质多样性,但其失调与神经退行性疾病有关.
- CELF2是一种拼接调节剂,也是阿尔茨海默病的风险因素.
研究的目的:
- 调查CELF2在调节Tau替代拼接中的作用及其与神经退行症的联系.
- 阐明CELF2控制陶外10拼接的机制.
主要方法:
- 在小鼠大脑模型中研究了CELF2与Tau mRNA的结合.
- 使用TurboID通过其内在无序区域 (IDR) 识别CELF2相互作用蛋白.
- 分析了CELF2突变和相互作用对Tau拼接的影响.
主要成果:
- 失去CELF2减少了Tau外10的含量,改变了4R:3R的比率.
- CELF2的IDR调解了凝析物形成和与NOVA2和SFPQ的相互作用.
- 在CELF2的IDR中保存的负电荷残留物 (D388) 对凝结物形成和拼接调节至关重要.
结论:
- CELF2通过使用NOVA2和SFPQ等拼接因子通过IDR介导的冷凝物形成来调节Tau的替代拼接.
- 这些凝结物中的蛋白质组成决定了替代拼接结果.
- 这种机制提供了关于CELF2在神经退行性疾病中的作用的见解.
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