m6A修饰抑制了miRNAs的细胞内功能,有利于它们的细胞外输出用于细胞间通信
Sabrina Garbo1, Daniel D'Andrea2, Alessio Colantoni3
1Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Department of Molecular Medicine, Sapienza University of Rome, Viale Regina Elena 324, 00161 Rome, Italy.
Cell reports
|June 15, 2024
概括
微RNA (miRNA) 中的N6-甲基氨酸 (m6A) 修饰会损害它们的功能,并促进它们被包装成细胞外囊泡 (EV) 以进行细胞间通信.
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.
- 细胞生物学 细胞生物学
背景情况:
- 包括N6-甲基氨酸 (m6A) 修饰在内的Epitranscriptomics,为基因表达调节增加了一层.
- 虽然m6A对microRNA (miRNA) 生成的影响已知,但对成熟的miRNA的影响尚不清楚.
研究的目的:
- 研究m6A修饰对成熟miRNAs的功能后果.
- 阐明m6A影响miRNA功能,局部化和细胞间转移的机制.
主要方法:
- 在特定的miRNA中分析m6A修饰.
- 对miRNA-AGO2相互作用和目标mRNA调节的评估.
- 通过RNA结合蛋白质对miRNA装载到细胞外囊泡 (EVs) 的研究.
- 通过FTO进行EV介导的miRNA转移和脱甲基化的功能研究.
主要成果:
- m6A 修改削弱了 miRNA 与 AGO2 的合,损害了细胞内功能.
- m6A通过 hnRNPA2B1 识别促进了miRNA 装载到 EVs 中.
- EV递送的miRNAs需要FTO介导的脱甲基化才能在受体细胞中发挥作用.
- 修改后的miRNAs作为细胞间信号而不是调节内源性点.
结论:
- m6A修饰调节成熟的miRNA功能和细胞间通信.
- 携带m6A修饰的EV包装的miRNAs作为细胞之间的调节信号.
- 这突出了由miRNAs的表体转录组修饰介导的细胞间通信的新机制.
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