Condensate functionalization with microtubule motors directs their nucleation in space and allows manipulating RNA localization

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. imageThere is a scarcity of available tools that allow the manipulation of cellular macromolecular condensates in a spatial manner. This study develops bioengineered motor-condensates, designed to drive the localization of RNA at the cell periphery or the centrosomes.Active ribonucleoprotein transport triggers local condensation.Motor condensates drive the delocalization of individual ASPM-MS2 mRNAs at the cell periphery.Motor condensates are versatile tools for altering the subcellular localization of RNA in living cells. In-cell reconstitution of a minimal ribonucleoprotein transport system provides new tools for redirecting RNA toward centrosomes or the cell periphery.image

Automated summary

This study develops a method to manipulate the localization of RNA in cells using bioengineered motor-condensates, thereby providing new tools for studying the impact of RNA localization on cellular functions.