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全长度直接RNA测序揭示了在细胞应激后的压力颗粒依赖RNA衰变
Showkat A Dar1, Sulochan Malla1, Vlastimil Martinek1,2,3
1Laboratory of Genetics and Genomics, National Institute on Aging, Intramural Research Program, National Institutes of Health, Baltimore, MD 21224, USA.
bioRxiv : the preprint server for biology
|September 11, 2023
概括
细胞应激会在5'端触发RNA衰变,影响转录组. 这个与翻译和压力颗粒相关的过程是XRN1依赖的,揭示了在压力期间RNA代谢的新见解.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 遗传学 是一个遗传学.
背景情况:
- 细胞激活应激反应途径,改变转录组的恒常性.
- RNA代谢在细胞应激反应中的作用至关重要,但尚未完全理解.
- 细胞应激期间RNA稳定性的全球变化仍然不清楚.
研究的目的:
- 在单分子分辨率下,在细胞应激期间全面分析人类转录组.
- 调查RNA稳定性的全球变化,并确定在压力下RNA衰变的机制.
主要方法:
- 使用纳米孔技术与5'端适配器绑定进行直接RNA测序.
- 开发一个统计框架来检测纳米孔数据中的RNA长度变化.
- 基因切除G3BP1和G3BP2以抑制压力颗粒的形成.
主要成果:
- 细胞应激诱导广泛的5'端RNA衰变,加上翻译和核糖体占用.
- 压力诱导的RNA衰变依赖于XRN1,但不依赖于死亡乙化或切割.
- 降解的RNA被富含压力颗粒;抑制压力颗粒的形成拯救了RNA的长度.
结论:
- 在细胞压力期间,RNA衰变是RNA代谢的关键决定因素.
- 压力诱导的RNA衰变取决于压力颗粒的形成.
- 这些发现挑战了典型的RNA衰变模型,并突出了一个新的调节机制.
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