Research News
TDP-43 Regulates Coupled Dendritic mRNA Transport-Translation Processes in Co-operation with FMRP and Staufen1
By Dr. Shen, Che-Kun James - December, 2019 Cell Reports 29, 3118–3133, December 3, 2019Tightly regulated transport of mRNP granules to diverse locations of dendrites and axons is essential for appropriately timed protein synthesis within distinct sub-neuronal compartments. Perturbations of this regulation lead to various neurological disorders. Using imaging and molecular approaches, including CRISPR/Cas9 mediated gene-tagging and the use of mRNA beacon, we demonstrate how TDP-43 co-operates with two other RNA-binding proteins, FMRP and Staufen1, to regulate the anterograde and retrograde transport, respectively, of Rac1 mRNPs in mouse neuronal dendrites. We also analyze the mechanisms by which TDP-43 mediates coupled mRNA transport-translation processes in dendritic sub-compartments by following in real-time the co-movement of RNA and endogenous fluorescence-tagged protein in neurons and by simultaneous examination of transport/translation dynamics by using an RNA biosensor. This study establishes the pivotal roles of TDP-43 in transporting mRNP granules in dendrites, inhibiting translation inside those granules, and reactivating it once the granules reach the dendritic spines.
