转录后对tRNA片段的修改使动脉样硬化中高密度脂蛋白发生功能变化
bioRxiv : the preprint server for biology
|January 7, 2025
概括
高密度脂蛋白 (HDL) 小RNA (sRNA) 上RNA修饰的变化与心血管疾病有关. 修改后的HDL-sRNAs促进了巨细胞的激活和细胞粘附,这表明它在疾病进展中的作用.
科学领域:
- 分子生物学分子生物学
- 心血管研究研究心血管研究
- 史诗转录组学 史诗转录组学
背景情况:
- 超转录性RNA的修改会影响RNA的稳定性,处理和功能.
- 在疾病期间,修饰小RNAs (sRNAs) 在无细胞高密度脂蛋白 (HDL) 中的作用尚不清楚.
- 在动脉样硬化心血管疾病 (ASCVD) 中,高密度胆固醇 (HDL) 失去有益的特性,可能是由于改变了高密度胆固醇-sRNAs.
研究的目的:
- 为了研究ASCVD中HDL-sRNAs上的RNA修饰的变化.
- 为了确定修改后的HDL-sRNAs对巨细胞行为的功能影响.
主要方法:
- 液体染色学-双重质谱法 (LC-MS/MS). 这是一个很好的方法.
- 由AlkB促进的RNA (去甲基化) 测序 (ABRFM-seq).
- 从健康和ASCVD受试者中分析HDL衍生的RNA.
- 使用原发性巨细胞和复合性HDL的功能性研究.
主要成果:
- 与ASCVD相关的HDL (ASCVD-HDL) 显示了改性核酸的丰富,特别是在tRNA衍生sRNA (tDRs) 上的m1A,特别是tDR-ArgACG-1.
- 在巨细胞中,ASCVD-HDL诱导的细胞粘附基因,包括TMEM123.
- 携带m1A-tDR-ArgACG-1的重组HDL上调了TMEM123并诱导了巨细胞中的免疫信号.
结论:
- HDL提供的m1A-tDR-ArgACG-1促进了巨细胞的激活.
- 这些发现表明,修改后的HDL-sRNAs通过影响粘附和免疫路径,有助于ASCVD病变的机制.
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