Injury-induced nuclear export of RNA-binding proteins drives mRNA stabilization and translation to promote dendrite...

Dendrite regeneration is critical for restoring neuronal connectivity after injury, yet the underlying molecular mechanisms remain poorly understood. Using C. elegans as a model and through a forward genetic screen, we identified the conserved insulin degrading enzyme idr-1 and the RNA-binding protein rbm-42 as key regulators of dendrite regeneration, where idr-1 functions upstream of rbm-42. We further show that ced-7, one of the core components of the phagocytosis pathway, acting down stream of rbm-42, while other components of this pathway don't play significant roles in dendrite regeneration. In addition, we demonstrate that upon injury IDR-1 can promote RBM-42 nuclear export following injury, enabling its dendritic localization. RBM-42, in turn, promotes the translation of ced-7 and facilitates microtubule assembly. In conclusion, our findings define a novel conserved signaling cascade coupling injury-induced nuclear export of RNA binding proteins to local regulation and dendrite regeneration, providing new mechanistic insight into neuronal repair.