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Condensate functionalization with microtubule motors directs their nucleation in space and allows manipulating RNA localization
The EMBO Journal ( IF 11.4 ) Pub Date : 2023-09-19 , DOI: 10.15252/embj.2023114106
Audrey Cochard 1, 2 , Adham Safieddine 2 , Pauline Combe 1 , Marie-Noëlle Benassy 2 , Dominique Weil 2 , Zoher Gueroui 1
Affiliation  

The localization of RNAs in cells is critical for many cellular processes. Whereas motor-driven transport of ribonucleoprotein (RNP) condensates plays a prominent role in RNA localization in cells, their study remains limited by the scarcity of available tools allowing to manipulate condensates in a spatial manner. To fill this gap, we reconstitute in cellula a minimal RNP transport system based on bioengineered condensates, which were functionalized with kinesins and dynein-like motors, allowing for their positioning at either the cell periphery or centrosomes. This targeting mostly occurs through the active transport of the condensate scaffolds, which leads to localized nucleation of phase-separated condensates. Then, programming the condensates to recruit specific mRNAs is able to shift the localization of these mRNAs toward the cell periphery or the centrosomes. Our method opens novel perspectives for examining the role of RNA localization as a driver of cellular functions.

中文翻译:

微管马达的凝结物功能化可引导其在空间中成核并允许操纵 RNA 定位

RNA 在细胞中的定位对于许多细胞过程至关重要。尽管核糖核蛋白 (RNP) 凝聚物的电机驱动运输在细胞中的 RNA 定位中发挥着重要作用,但他们的研究仍然受到缺乏允许以空间方式操纵凝聚物的可用工具的限制。为了填补这一空白,我们在细胞中重建了一个基于生物工程冷凝物的最小 RNP 运输系统,该系统通过驱动蛋白和动力蛋白样马达进行功能化,允许它们定位在细胞外围或中心体。这种靶向主要通过冷凝物支架的主动运输发生,这导致相分离冷凝物的局部成核。然后,对浓缩物进行编程以招募特定的 mRNA,能够将这些 mRNA 的定位转向细胞外周或中心体。我们的方法为研究 RNA 定位作为细胞功能驱动因素的作用开辟了新的视角。
更新日期:2023-09-19
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