(129d) A Synthetic Device for Intracellular mRNA Transport and Local Protein Translation in Eukaryotes

Intracellular mRNA transport and local protein translation are thought to play a crucial role in numerous cellular processes in eukaryotes, including cell migration during embryogenesis, innate immune response, bone and connective tissue remodeling, and many neurological processes. Synthetic devices capable of controlling directional mRNA transport and allowing user-defined local protein translation could be useful in fundamental research as well as provide therapeutic solutions for neurodegenerative disorders that involve disrupted mRNA transport into neurites. In this work, we created a biosynthetic device for RNA transport that consists of two components: a “motor”, which provides a directional movement, and an RNA-binding protein that heterodimerizes with the “motor” in a ligand-dependent manner. We observed ligand-dependent, motor-specific transport and co-localization of the RNA-binding protein and target mRNA only in the presence of binding sites in the 3’ UTR of mRNA in HeLa cells. We are working on further engineering of this system for local protein translation of reporter and endogenous human genes. We believe that this prototypical synthetic device will allow easy and controlled intracellular mRNA transport regulation in eukaryotes and will eventually be helpful in basic science and therapeutics.