非正规的开放阅读框架的翻译控制了粘膜免疫力
Ruaidhrí Jackson1, Lina Kroehling1, Alexandra Khitun2
1Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA.
Nature
|December 14, 2018
概括
科学家们发现许多以前认为非蛋白质编码的RNA分子实际上产生了功能性蛋白质. 这些新型蛋白质对于细菌感染和其他疾病的免疫反应至关重要.
科学领域:
- 基因组学
- 免疫学
- 分子生物学
背景情况:
- 目前对哺乳动物蛋白质编码基因组的注释是不完整的.
- 鉴定蛋白质编码基因的传统方法依赖于特定的标准 (例如ORF大小,ATG启动),这些标准可能会排除新功能转录.
- 非正规的开放阅读框架 (ORF) 编码功能蛋白质的潜力是一个正在进行的研究和辩论领域.
研究的目的:
- 调查以前标注为非编码的RNA的蛋白质编码潜力.
- 识别非正规ORF产生的新型功能蛋白.
- 确定这些新发现的蛋白质在免疫反应中的作用.
主要方法:
- 在对细菌感染作出反应的巨细胞中采用了无偏向的转录基因方法.
- 使用核糖体分析来识别活跃翻译的RNA,包括非正规的ORF.
- 进行了功能性研究以评估非正规ORF转化蛋白的作用.
主要成果:
- 发现大量注释为非蛋白质编码的RNA与核糖体结合,表明活性翻译.
- 鉴定出能够产生稳定和独特的蛋白质的短和非ATG发起的ORF.
- 在长非编码RNA Aw112010中发现了一种新型的ORF,对于在细菌感染和大肠炎期间协调粘膜免疫力至关重要.
结论:
- 哺乳动物基因组的蛋白质编码潜力比以前理解的更广泛,包括非正规的ORF.
- 从非正规的ORF转化出来的蛋白质在免疫反应中起着至关重要的作用.
- 非编码RNA的错误注释可能会掩盖未发现的蛋白质编码基因在免疫和疾病中的功能.
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