以后翻译修改为中心的基础编辑器屏幕,以评估高吞吐量酸化站点的功能.
Patrick H Kennedy1,2,3, Amin Alborzian Deh Sheikh1,2,3, Matthew Balakar4
1Laboratory for Immunochemical Circuits, La Jolla Institute for Immunology, La Jolla, CA, USA.
Nature methods
|April 29, 2024
概括
科学家们开发了一种新方法来研究数千种动态后翻译性修饰 (PTM) 和它们在基因表达中的作用. 这种方法揭示了以前未知的酸化部位,可以微调细胞信号通路.
科学领域:
- 分子生物学分子生物学
- 细胞信号传输 细胞信号传输
- 基因组学就是基因组学.
背景情况:
- 细胞功能是由成千上万的动态后翻译性修改 (PTM) 协调的,但将这些修改与基因电路连接起来的技术在规模上是有限的.
- 目前对信号通路的理解往往集中在有限数量的关键酸化和转录事件上,忽视了PTM的复杂性.
研究的目的:
- 开发一种高通量方法,用于评估酸化部位对细胞过程的功能影响.
- 研究未研究的酸化部位在T细胞激活和转录调节中的作用.
主要方法:
- 开发以PTM为中心的基础编辑与表型查相结合.
- 暂时解决的蛋白质组的应用,以指导功能评估.
- 利用T细胞激活作为研究信号通路的模型系统.
主要成果:
- 确定了数百个以前未被研究的酸化位,这些位调节激活T细胞核因子 (NFAT) 转录活性.
- 发现酸化调解PHLPP1的核定位,影响NFAT和核因子kappa B (NFκB) 活动.
- 证明特定的酸突变可以微妙地改变基因表达模式,表明对微调转录反应的能力.
结论:
- 基础编辑器对PTM站点的选提供了一个强大的平台,可以在复杂的信号通路中剖析翻译后修改的功能角色.
- 这些发现突出了许多酸化事件对细胞调节和基因表达的显著,但往往被忽视的贡献.
相关概念视频
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