The kpc-1 3′UTR facilitates dendritic transport and translation efficiency of mRNAs for dendrite arborization of a mechanosensory neuron important for male courtship.

A recently reported Schizophrenia-associated genetic variant in the 3′UTR of the human furin gene, a homolog of C. elegans kpc-1, highlights an important role of the furin 3′UTR in neuronal development. We isolate three kpc-1 mutants that display abnormal dendrite arborization in PVD neurons and defective male mating behaviors. We show that the kpc-1 3′UTR participates in dendrite branching and self-avoidance. The kpc-1 3′UTR facilitates mRNA localization to branching points and contact points between sibling dendrites and promotes translation efficiency. A predicted secondary structural motif in the kpc-1 3′UTR is required for dendrite self-avoidance. Animals with over-expression of DMA-1, a PVD dendrite receptor, exhibit similar dendrite branching and self-avoidance defects that are suppressed with kpc-1 over-expression. Our results support a model in which KPC-1 proteins are synthesized at branching points and contact points to locally down-regulate DMA-1 receptors to promote dendrite branching and self-avoidance of a mechanosensory neuron important for male courtship. Author summary: Here, we report a non-coding sequence immediately downstream of the kpc-1 gene participating in the transport and, subsequently, the translation of the kpc-1 messenger RNA in the nerve process of a mechanosensory neuron, which is required to establish a functional neuronal circuit regulating the male mating behavior in C. elegans. Interestingly, a human Schizophrenia-associated mutation located in the non-coding sequence immediately downstream of the human furin gene, a kpc-1 homologous gene, was recently shown to contribute to the pathogenesis of Schizophrenia. By analogy, whether this human furin downstream mutation disrupts the transport and the translation of the furin mRNA in the nerve process of Schizophrenia-causing neurons during its differentiation remains to be seen. [ABSTRACT FROM AUTHOR]

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