Roles of intron retention and splicing factors in axons

In our nervous system, neurons transport mRNAs (transcripts) along axons and dendrites, where they are translated into proteins, centimeters away from their cell body. Dysfunctions in this mechanism are associated to human neurological and neurodegenerative disorders. We recently discovered that the diversity of axonal transcripts depends upon two axonally-located splicing proteins. Yet, these proteins were so far known for transforming draft mRNA into mature transcripts in the cell nucleus, their role on mRNA in neurites being unexplored. We also found that some axonal mRNAs are partially immature (still containing a piece of "draft" RNA called intron). We propose to i) understand how splicing proteins modulate axonal mRNA diversity, ii) reveal what introns do in axons, and iii) discover the functional links between introns and splicing proteins in axons. We will answer these essential questions, at cellular and molecular levels, using zebrafish animals and primary neuronal cultures as experimental models.