Inducible Control of mRNA Transport Using Reprogrammable RNA-Binding Proteins

Localization of mRNA is important in a number of cellular processes such as embryogenesis, cellular motility, polarity, and a variety of neurological processes. A synthetic device that controls cellular mRNA localization would facilitate investigations on the significance of mRNA localization in cellular function and allow an additional level of controlling gene expression. In this work, we developed the PUF (Pumilio and FBF homology domain)-assisted localization of RNA (PULR) system, which utilizes a eukaryotic cell's cytoskeletal transport machinery to reposition mRNA within a cell. Depending on the cellular motor used, we show ligand-dependent transport of mRNA toward either pole of the microtubular network of cultured cells. In addition, implementation of the reprogrammable PUF domain allowed the transport of untagged endogenous mRNA in primary neurons.