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CELF RNA binding proteins promote axon regeneration in C. elegans and mouse through regulation of syntaxin

ABSTRACT: Axon injury triggers dramatic changes in gene expression. While transcriptional regulation of injury-induced gene expression is widely studied, less is known about the roles of RNA binding proteins (RBPs) in post-transcriptional regulation during axon regeneration. In C. elegans the CELF (CUGBP and Etr-3 Like Factor) family RBP UNC-75 is required for axon regeneration. Using crosslinking immunoprecipitation coupled with deep sequencing (CLIP-seq) we identify a set of genes involved in synaptic transmission as mRNA targets of UNC-75. In particular, we show that UNC-75 regulates alternative splicing of two mRNA isoforms of the SNARE syntaxin/unc-64. In C. elegans mutants lacking unc-75 or its targets, regenerating axons form growth cones, yet are deficient in extension. Extending these findings to mammalian axon regeneration, we show that mouse Celf2 expression is upregulated after peripheral nerve injury and that Celf2 mutant mice are defective in axon regeneration. CLIP-seq and expression analysis also reveal CELF2 dependent regulation of selective syntaxins. Our data delineate a post-transcriptional regulatory pathway with a conserved role in regenerative axon extension.

ORGANISM(S): Caenorhabditis elegans Mus musculus

PROVIDER: GSE78111 | GEO | 2016/06/02

SECONDARY ACCESSION(S): PRJNA312625

REPOSITORIES: GEO

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