通过全转录组 snoRNA 标识发现 snoRNA 促进的蛋白质分泌
Bei Liu1, Tong Wu1, Bernadette A Miao2
1Department of Chemistry, The University of Chicago, Chicago, IL 60637, USA; Howard Hughes Medical Institute, Chicago, IL 60637, USA.
Cell
|November 23, 2024
概括
小核RNAs (snoRNAs) 可以针对传递 RNAs (mRNAs) 的非正规功能. 一种新的化学交联方法揭示了数千种snoRNA-mRNA相互作用,包括SNORA73促进蛋白质分泌.
科学领域:
- 分子生物学
- 核糖核酸生物学
- 基因组学
背景情况:
- 小核RNAs (snoRNAs) 主要以指导RNA修饰,如2'-O-甲基化和伪尿素.
- 由于技术的局限性,斯诺RNA,特别是信使RNA (mRNA) 的全部RNA目标范围尚不清楚.
- 广泛识别snoRNA目标对于理解它们在RNA修饰之外的多样性细胞作用至关重要.
研究的目的:
- 开发和应用一种基于化学交联的新技术,以全面识别snoRNA目标.
- 发现以前未知的snoRNA与其他细胞RNA,特别是mRNA之间的相互作用.
- 调查已识别的snoRNA-mRNA相互作用的功能影响,特别是非正规的作用.
主要方法:
- 开发一种基于化学交联的方法来捕获和识别RNA-RNA相互作用.
- 该方法应用于人类细胞和小鼠脑组织以检测snoRNA标.
- 生物信息分析以识别和量化全转录组的snoRNA-mRNA相互作用.
主要成果:
- 在人类细胞和小鼠大脑中发现了数千种以前未知的snoRNA-mRNA相互作用.
- 这些相互作用的很大一部分发生在已知的snoRNA导向RNA修饰部位之外,这表明非正规的功能.
- 发现 snoRNA SNORA73 的目标是编码分泌和膜蛋白的 mRNA,并与信号识别粒子 (SRP) 的 7SL RNA 相互作用.
结论:
- 开发的化学交联方法有效地识别了大量的snoRNA-RNA相互作用,扩大了snoRNA的已知目标.
- SnoRNA参与非正规功能,与mRNA和其他RNA如7SLRNA相互作用,影响细胞过程.
- 使用SNORA73与目标mRNA和7SLRNA的相互作用来增强SRP关联,从而促进编码蛋白质的分泌.
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