在人类转录基因组中系统地搜索RNA结构开关.
Matvei Khoroshkin1,2,3,4, Daniel Asarnow1,5, Shaopu Zhou1,2,3,4
1Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA.
Nature methods
|July 16, 2024
概括
SwitchSeeker在人类中发现了新的RNA结构开关,揭示了它们在基因调节中的作用. 该方法使用计算和实验技术来发现这些关键元素及其对基因表达的影响.
科学领域:
- 分子生物学分子生物学
- 基因组学就是基因组学.
- 生物信息学是一种生物信息学.
背景情况:
- RNA结构开关调节细菌中的基因表达,但在Metazoa中了解甚少.
- 在真核生物中缺乏功能性RNA结构开关的系统识别.
研究的目的:
- 开发和验证一个全面的计算和实验方法,SwitchSeeker,用于识别人类转录组中的功能RNA结构开关.
- 描述RORC转录中的一种新型RNA结构开关,并研究其调节机制.
主要方法:
- 将SwitchSeeker应用于人类转录组,以识别假定的RNA开关.
- 在体内进行二甲基硫酸盐基因突变分析,使用测序 (DMS-MaPseq) 和冷电子显微镜进行结构验证.
- 基因组规模的CRISPR屏幕用于识别调节RNA结构开关的转作用因子.
主要成果:
- 在人类转录组中识别了245个假定的RNA结构开关.
- 在RORC 3'未翻译区域的新型开关的表征,存在于两种替代构造.
- 发现无意义介导的信使RNA衰变以特定的形式调节这种开关.
结论:
- SwitchSeeker 是一种有效的,公正的,实验驱动的方法,用于发现真核生物中的RNA结构开关.
- RNA结构开关在塑造真核细胞基因表达格局方面发挥着重要作用.
- 转变因子的特定调节,包括无意义介导的信使RNA衰变,突显了基于RNA的基因控制的复杂性.
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