RNA AND CYTOSKELETAL FUNCTIONS OF EXON JUNCTION COMPLEX COMPONENTS IN NEURONAL DENDRITOGENESIS

The exon junction complex (EJC) is a protein complex that acts as a central mRNA regulator in eukaryotic cells by controlling splicing, export, translation and nonsense-mediated decay. The core EJC components EIF4A3, MAGOH, and RBM8A are crucial for neurogenesis, where they work together in neural differentiation by regulating gene expression of common molecular pathways. Interestingly, we recently demonstrated that EIF4A3, the nucleating component of the EJC, plays a non-canonical role in axon growth during neuronal maturation by directly binding to microtubules, promoting their polymerization. However, it is unknown whether EJC components regulate later stages of neuronal development such as dendritogenesis, and if such regulation occurs via RNA/EJC binding or independently through non-canonical functions. Therefore, we sought to determine dendrite outgrowth in Eif4a3, Rbm8a or Magoh-depleted mouse cortical neurons at different days in vitro. We also are analyzing the dendritic arborization in vivo of Eif4a3-, Rbm8a- or Magoh-conditional knockout mice and the neuronal transcriptomic profile of these EJC mutants at different embryonic and postnatal timepoints. To assess a potential cytoskeletal function of EIF4A3 in dendrite growth, we are characterizing microtubule dynamics by live-imaging using microtubule growth reporters. Our results indicate that core EJC components may have divergent roles at different stages of neural development. This continuing project will define how core EJC components control gene expression and microtubule dynamics during neuronal development. By addressing this knowledge gap, we may uncover a new paradigm for how mRNA metabolism and cytoskeletal dynamics control neuronal function across the stages of neuronal development.