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功能性微RNA吸收和线粒体递送的新途径
Jiachen Liu1, Weili Li1, Jianfeng Li1
1State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University School of Life Sciences, Nanjing, Jiangsu, 210093, China.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
|June 25, 2023
概括
细胞外微RNAs (miRNAs) 自己组装成纳米粒子以供细胞吸收. 这种新的途径将功能性miRNA送入线粒体,影响细胞能量和活性氧物种水平.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- 细胞外微RNAs (miRNAs) 是基因表达的关键调节者.
- 细胞外miRNA吸收和细胞内贩运的机制尚未完全理解.
研究的目的:
- 研究一种用于细胞外miRNA吸收和细胞内传递的新途径.
- 阐明RNA相分离在miRNA内化中的作用.
主要方法:
- 合成miRNAs与血清进行化,以观察自组装成纳米粒子.
- 血清阴离子蛋白被耗尽,以评估它们在纳米粒子形成中的作用.
- 使用各种细胞模型分析了miRNA吸收和细胞内定位.
- 进行了功能性测试,以评估内部化miRNAs对线粒体功能的影响.
主要成果:
- 细胞外miRNA通过RNA相分离在血清中自发形成纳米粒子 (≈110nm).
- 血清阴离子蛋白对于miRNA纳米颗粒的形成和随后的细胞吸收至关重要.
- 纳米粒子介导的miRNA吸收主要将miRNA输送到线粒体中,依赖于聚核酸核转移酶1 (PNPT1).
- 内部化的miR-21增强了细胞染色体b (CYB) 的线粒体翻译,增加了ATP的产生,减少了活性氧物种 (ROS).
结论:
- RNA相分离代表了细胞外miRNA吸收的新机制.
- 这一途径促进了功能性miRNAs在细胞线粒体中的有针对性的输送.
- 这些发现揭示了基于miRNA的基因调控影响线粒体生物能学的新途径.
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