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在活细胞中光遗传学控制 mRNA 的定位和翻译。

Optogenetic control of mRNA localization and translation in live cells.

机构信息

Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea.

Center for Cognition and Sociality, Institute for Basic Science (IBS), Daejeon, Republic of Korea.

出版信息

Nat Cell Biol. 2020 Mar;22(3):341-352. doi: 10.1038/s41556-020-0468-1. Epub 2020 Feb 17.

Abstract

Despite efforts to visualize the spatio-temporal dynamics of single messenger RNAs, the ability to precisely control their function has lagged. This study presents an optogenetic approach for manipulating the localization and translation of specific mRNAs by trapping them in clusters. This clustering greatly amplified reporter signals, enabling endogenous RNA-protein interactions to be clearly visualized in single cells. Functionally, this sequestration reduced the ability of mRNAs to access ribosomes, markedly attenuating protein synthesis. A spatio-temporally resolved analysis indicated that sequestration of endogenous β-actin mRNA attenuated cell motility through the regulation of focal-adhesion dynamics. These results suggest a mechanism highlighting the indispensable role of newly synthesized β-actin protein for efficient cell migration. This platform may be broadly applicable for use in investigating the spatio-temporal activities of specific mRNAs in various biological processes.

摘要

尽管人们努力可视化单个信使 RNA 的时空动态,但精确控制其功能的能力却一直滞后。本研究提出了一种光遗传学方法,通过将特定的 mRNA 困在簇中,来操纵它们的定位和翻译。这种聚类极大地放大了报告信号,使内源性 RNA-蛋白质相互作用能够在单细胞中清晰地可视化。在功能上,这种隔离降低了 mRNA 与核糖体结合的能力,显著抑制了蛋白质合成。时空分辨分析表明,β-actin mRNA 的隔离通过调节焦点黏附动力学,减弱了细胞的迁移能力。这些结果表明了一种机制,突出了新合成的β-actin 蛋白对有效细胞迁移的不可或缺的作用。该平台可能广泛适用于研究各种生物过程中特定 mRNA 的时空活性。

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