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TDRD3作为选择性自受体,在自和压力颗粒稳定性调节方面具有双重作用
Matthew Deater1, Richard E Lloyd1
1Department of Molecular Virology and Immunology, Baylor College of Medicine, Houston, TX 77030.
bioRxiv : the preprint server for biology
|September 30, 2024
概括
含有Tudor域3 (TDRD3) 作为一种自受体,类似于p62/SQSTM1,调节应力颗粒的稳定性和周转. 它通过LIR动机与LC3B的相互作用对这些过程和病毒复制至关重要.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 病毒学 病毒学
背景情况:
- 含有Tudor域3 (TDRD3) 是一个参与转录的核甲基氨酸读取器.
- 在综合应激反应 (ISR) 过程中,TDRD3被招募到应激颗粒 (SG),但其功能尚不清楚.
- 肠道病毒劫持自细胞进行复制,而TDRD3是一种已知的抗病毒因子,由病毒蛋白酶分裂.
研究的目的:
- 研究TDRD3在选择性自中的作用.
- 为了确定TDRD3是否作为选择性自受体起作用.
- 阐明TDRD3在应力颗粒中的功能及其与自机械的相互作用.
主要方法:
- 在HeLa细胞中敲除 (KO) 和重新引入TDRD3.
- 使用显微镜和共免疫沉 (coIP) 分析自标记物 (LC3B,p62/SQSTM1,Lamp2).
- 创建和测试缺乏UBA或LIR动机的TDRD3删除突变.
- 超分辨率显微镜和化物诱导的应力颗粒试验.
主要成果:
- TDRD3 KO减少了饥饿诱导的自;重新引入恢复了剂量取决于它.
- 在自过程中,TDRD3水平下降,类似于p62/SQSTM1,这表明了目标周转.
- 删除TDRD3突变体 (ΔLIR) 在LC3B和Lamp2的同位化中显示出缺陷.
- TDRD3变种破坏了SG凝聚和改变了SG衰变动力学;LIR3动机是LC3B相互作用和SG招募/解决的关键.
结论:
- TDRD3作为一种选择性自受体,类似于p62/SQSTM1.
- TDRD3在应力颗粒的稳定性和周转方面发挥着作用.
- 肠道病毒对TDRD3的分裂影响了对病毒复制至关重要的抗病毒和自反应.
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