PCBP1/2和TDP43 作为NAT10适配器的功能,以调解哺乳动物细胞中的mRNAac4C形成
Zhi-Yan Jiang1,2, Yu-Ke Wu2, Zuo-Qi Deng2
1Zhejiang Key Laboratory of Precise Protection and Promotion of Fertility, Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310016, China.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
|November 18, 2024
概括
研究人员确定了一组复杂的蛋白质,包括NAT10,PCBP1/2和TDP43,在哺乳动物细胞中调解mRNA乙化 (ac4C). 这一发现澄清了mRNA乙化是如何发生的,并影响了特定的RNA序列.
科学领域:
- 分子生物学分子生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 在RNA代谢过程中.
背景情况:
- 在mRNA中修改基,形成表转录组,对于RNA代谢至关重要.
- N-4-乙基丁 (ac4C) 是唯一已知的乙化RNA修饰,在物种中保存.
- 此前,GCN5相关的乙转移酶10 (NAT10) 酶对ac4C形成的精确机制尚不清楚.
研究的目的:
- 通过确定负责ac4C形成的蛋白质复合体来阐明mRNA乙化的机制.
- 了解RNA结合蛋白在招募NAT10到特定mRNA点中的作用.
主要方法:
- 研究了哺乳动物细胞中NAT10和RNA结合蛋白 (RBPs) 之间的相互作用.
- 利用HEK293T细胞的淘汰实验来评估RBPs对mRNA乙化的影响.
- 分析了RBPs对NAT10向特定mRNA序列的招募的影响.
主要成果:
- 鉴定了一种复合体,包括NAT10,多C结合蛋白1/2 (PCBP1/2),和TAR DNA结合蛋白43 (TDP43),该复合体介导mRNAac4C形成.
- 证明PCBP1/2和TDP43充当适配器,将NAT10与mRNA基质结合起来.
- 观察到mRNA乙化减少和在适应器敲击时失去特定的ac4C动机.
- 表明这些适配器将NAT10招募到它们的结合部位,从而影响ACC部位选择.
结论:
- NAT10/PCBP/TDP43复合体是哺乳动物细胞中mRNAac4C形成的主要媒介.
- PCBP1/2和TDP43在mRNA乙化中的基质选择和局部化中发挥着关键作用.
- 这些发现提供了关于表表写体的调节和mRNA乙化的生理相关性的见解,特别是在像小鼠丸这样的环境中.
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