调控哺乳动物TRIM71蛋白的RNA结合性能的分子机制
Fandi Shi1, Kun Zhang1, Qixuan Cheng2
1State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Nankai University, Tianjin 300353, China.
Science bulletin
|November 30, 2023
概括
研究人员确定了TRIM71识别的特定RNA基因,TRIM71是细胞周期和干细胞调节至关重要的蛋白质. 这一发现揭示了TRIM71如何与RNA结合,为TRIM71相关疾病提供了洞察力.
科学领域:
- 分子生物学分子生物学
- 结构生物学 结构生物学
- 遗传学 遗传学 是一个
背景情况:
- TRIM71是一种RNA结合蛋白,调节细胞循环和干细胞自我更新等关键细胞过程.
- 它的RNA结合性质是其多样化的功能的核心.
- 以前的研究表明TRIM71与lncRNATrincr1相互作用,以控制小鼠胚胎干细胞 (mESC) 中的FGF/ERK通路.
研究的目的:
- 阐明哺乳动物TRIM71.1.通过RNA识别的分子机制.
- 为了确定TRIM71-RNA相互作用的特定RNA动机和结构基础.
- 了解TRIM71-RNA结合在细胞过程和疾病中的功能影响.
主要方法:
- 从Trincr1 RNA中识别RNA基因.
- 结晶结构的确定 mTRIM71 NHL域复杂的RNA动机.
- 在mRNA UTRs中映射TRIM71结合的毛RNAs.
- 位点定向突变发生,以评估关键TRIM71残留物和CH特异性突变在RNA结合中的作用.
主要成果:
- 来自Trincr1的RNA干循环基因,在循环中具有关键的腺,被确定为mTRIM71.1.的特定结合部位.
- 晶体结构揭示了mTRIM71的NHL域与RNA图案的复杂性.
- 在TRIM71.1.调节的细胞循环基因的UTR中发现了类似的针头RNA.
- 在mTRIM71中发现了关键的保存残留物,这些残留物对于头RNA结合至关重要,无论是在体外还是在mESC中.
- 在mTRIM71中,与先天性水脑 (CH) 相关的突变损害了其RNA结合.
结论:
- 这项研究揭示了哺乳动物TRIM71识别特定RNA毛结构的分子基础.
- 这些发现凸显了保留残留物和特异性RNA动机在TRIM71功能中的重要性.
- 了解TRIM71-RNA相互作用为TRIM71相关的发育障碍提供了关键的见解,例如先天性水头.
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