Elavl3 regulates neuronal polarity through the alternative splicing of an embryo-specific exon in AnkyrinG

Alternative splicing of RNAs diversifies the functionalities of proteins, and it is optimized for each cell type and each developmental stage. nElavl (composed of Elav12, Elavl3, and Elav14) proteins are the RNA-binding proteins that is specifically expressed in neurons, regulate the alternative splicing of target RNAs, and promote neuronal differentiation and maturation. Recent studies revealed that ElavI3 knockout (Elavl3(-/-)) mice completely lost the expression of nElavl proteins in the Purkinje cells and exhibited cerebellar dysfunction. Here, we found that the alternative splicing of AnkyrinG exon 34 was misregulated in the cerebella of Elav13(-/-)mice. AnkyrinG is an essential factor for the formation of neuronal polarity and is required for normal neuronal functions. We revealed that exon 34 of AnkyrinG was normally included in immature neurons and was mostly excluded in mature neurons; however, it was included in the cerebella of Elav13(-/-)mice even in adulthood. In the Purkinje cells of adult Elav13(-/-)mice, the length of the AnkyrinG-positive region shortened and somatic organelles leaked into the axons. These results suggested that exon 34 of AnkyrinG is an embryonic-stage-preferential exon that should be excluded from mature neurons and that Elavl3 regulates neuronal polarity through alternative splicing of this exon. (C) 2018 Elsevier B.V. and Japan Neuroscience Society. All rights reserved.