AGENDA

Title : A Molecular Code for Extracellular RNA Trafficking
Contact : robert.feil@igmm.cnrs.fr
 
Abstract: 
Cells exchange information not only through hormones, neurotransmitters, and small molecules, but also via RNAs that cross cellular boundaries. Cell-to-cell RNA communication has been implicated in the modulation of brain development and function, yet the mechanisms that govern the selective transfer of specific RNAs are unknown. Using genome-wide CRISPR screening, proteomics, and high-sensitivity transcriptomics in a neuronal cell line, we identify domesticated retroviral proteins and RNA-modifying enzymes that regulate neuronal RNA loading into and transportation via extracellular vesicles. We show that the pseudouridine synthase PUS1 is a key determinant of RNA trafficking, and that its catalytic product in RNA, pseudouridine, is both necessary and sufficient for extracellular RNA export. We further show that myosin light chain 6 (MYL6) is a pseudouridine-binding protein required for secretion of synthetic and endogenous RNAs.These findings reveal a biochemical code linking chemical RNA modification to extracellular transport, and establish a framework to study the function of extracellular RNAs in the nervous system.