RNAlocalization and co-translational interactions controlRAB13GTPase function and cell migration

NumerousRNAs exhibit specific distribution patterns in mammalian cells. However, the functional and mechanistic consequences are relatively unknown. Here, we investigate the functional role ofRNAlocalization at cellular protrusions of migrating mesenchymal cells, using as a model theRAB13RNA, which encodes aGTPase important for vesicle-mediated membrane trafficking. WhileRAB13RNAis enriched at peripheral protrusions, the expressed protein is concentrated perinuclearly. By specifically preventingRAB13RNAlocalization, we show that peripheralRAB13 translation is not important for the overall distribution of theRAB13 protein or its ability to associate with membranes, but is required for full activation of theGTPase and for efficient cell migration.RAB13 translation leads to a co-translational association of nascentRAB13 with the exchange factorRABIF. Our results indicate thatRAB13-RABIFassociation at the periphery is required for directingRAB13GTPase activity to promote cell migration. Thus, translation ofRAB13 in specific subcellular environments imparts the protein with distinct properties and highlights a means of controlling protein function through localRNAtranslation.