非正规的人类开放阅读框架的普遍功能翻译
Jin Chen1,2, Andreas-David Brunner3, J Zachery Cogan1,2
1Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158, USA.
概括
研究人员在人类细胞中发现了数百种重要的微蛋白, 这些微蛋白具有多种作用,包括免疫系统的呈现和与已知的蛋白质形成复合物.
科学领域:
- 分子生物学
- 基因组学
- 人类生理学
背景情况:
- 核糖体分析表明翻译发生在正规编码序列 (CDS) 之外,但这些序列在很大程度上没有特征.
- 这些非正典翻译的功能意义和细胞作用在很大程度上是未知的.
研究的目的:
- 系统地识别和描述人类细胞中的非正规编码序列 (CDS) 和它们编码的微蛋白.
- 研究这些新发现的微蛋白的细胞功能,定位和相互作用.
主要方法:
- 使用基于CRISPR的系统查策略来识别非正规的CDS.
- 进行功能性表征,包括细胞局部化,蛋白质与蛋白质相互作用研究,以及人类白细胞抗原 (HLA) 系统的呈现分析.
主要成果:
- 识别了数百种对细胞生长至关重要的非正规的CDS.
- 这些CDS的破坏导致了特定的转录和表型变化.
- 这些CDS编码的特征微蛋白,揭示了不同的局部,结合伙伴和HLA呈现.
- 发现了在上游开放读取 (uORF) 中编码的微蛋白,形成与正规蛋白的功能双子.
结论:
- 人类细胞利用大量的功能性微蛋白编码在正规CDS之外.
- 这些微蛋白在细胞功能中起到关键和多样化的作用,包括蛋白质复合体的形成和免疫监测.
- 在哺乳动物中识别功能性双子扩大了我们对基因调节和蛋白质生产的理解.
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