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Publication : TDP-43 Regulates Coupled Dendritic mRNA Transport-Translation Processes in Co-operation with FMRP and Staufen1.

First Author  Chu JF Year  2019
Journal  Cell Rep Volume  29
Issue  10 Pages  3118-3133.e6
PubMed ID  31801077 Mgi Jnum  J:300864
Mgi Id  MGI:6488964 Doi  10.1016/j.celrep.2019.10.061
Citation  Chu JF, et al. (2019) TDP-43 Regulates Coupled Dendritic mRNA Transport-Translation Processes in Co-operation with FMRP and Staufen1. Cell Rep 29(10):3118-3133.e6
abstractText  Tightly regulated transport of messenger ribonucleoprotein (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, 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.
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