Société Française de Biochimie et Biologie Moléculaire

Audrey Cochard - November 2023

IBPS, ENS, Paris "Condensate functionalization with microtubule motors directs their nucleation in space and allows manipulating RNA localization"
The EMBO Journal (2023)
Audrey Cochard, Adham Safieddine, Pauline Combe, Marie-Noëlle Benassy, Dominique Weil, Zoher Gueroui


Audrey Cochard, 28 years old, was a Ph.D. student under the direction of Zoher Gueroui of the Department of Chemistry of the ENS Paris, and of Dominique Weil of the Institute of Biology Paris-Seine of Sorbonne University. Her Ph.D. project concerned biomolecular condensates, which are membraneless organelles taking part in the intracellular organization. Because of the biochemical complexity of endogenous condensates, reconstitution approaches in cells of artificial condensates with controlled composition are required. In this article published in EMBO Journal, Audrey Cochard and her collaborators have developed a method to functionalize artificial condensates in cells with molecular motors. They first showed the possibility of controlling the localization of condensates nucleation, either at the cell periphery or at the centrosome, depending on the molecular motor. This system then allowed them to modify the localization of a target RNA, heterologously expressed or endogenous, by recruiting it specifically in the artificial condensates. This method opens multiple possibilities for the study of RNA subcellular localization importance.
Audrey is now a postdoctoral researcher in the Biomedical Microsystems laboratory at the Institute of Industrial Science in the University of Tokyo in Japan.


SH Kim laboratory, Institute of Industrial Science, Tokyo University.

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Résumé de l'article

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.