终结编码对NNAT mRNA的透读调节介导的神经元分化
Madhuparna Pandit1, Md Noor Akhtar1, Susinder Sundaram1
1Department of Biochemistry, Indian Institute of Science, Bengaluru, Karnataka, India.
The Journal of biological chemistry
|August 23, 2023
概括
在NNAT mRNA中,终结密码子通读 (TCR) 产生一种非功能性蛋白质异型 (NNATx),阻碍神经元分化. 用反感性寡核酸调节TCR可以增强胆固醇神经元的发育.
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.
- 细胞生物学 细胞生物学
背景情况:
- 终结密码子读透 (TCR) 产生C端扩展的蛋白质异型.
- NNAT编码了一种对神经元分化至关重要的蛋白质脂质.
- 一种RNA结合蛋白NONO可以负面调节NNAT TCR.
研究的目的:
- 为了研究哺乳动物NNAT mRNA中的编程TCR.
- 为了确定TCR产品 (NNATx) 对神经元差异化的功能影响.
- 探索NNAT TCR对治疗应用的调制.
主要方法:
- 使用哺乳动物细胞模型在NNAT mRNA中证明TCR.
- 生物化学测试以评估NNATx与Ca2+和细胞质Ca2+水平的相互作用.
- 反感性寡核酸 (ASO) 治疗以抑制NNAT TCR.
- 在CRISPR-Cas9基因编辑中创建NNATx缺陷细胞.
主要成果:
- NNAT mRNA经过编程的TCR,产生NNATx.
- NNATx与SERCA2a没有相互作用,无法增加细胞质Ca2+,并且不促进神经元分化.
- 针对停止编码子下游的NNAT mRNA的ASO治疗减少了TCR并增强了Neuro-2a细胞分化.
- 缺乏NNATx的细胞表现出高细胞质Ca2+和增强的分化.
结论:
- NNAT 的 TCR 调节神经元分化.
- 该NNATx异型在功能上与正规NNAT不同,并且抑制了分化.
- 合成ASO可以调节NNAT TCR,提供一种增强神经元分化的潜在策略.
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