Post-transcriptional regulation of adult CNS axonal regeneration by Cpeb1

ABSTRACT Adult mammalian CNS neurons are unable to regenerate following axonal injury, leading to permanent functional impairments. Yet, the reasons underlying this regeneration failure are not fully understood. Here, we study the transcriptome and proteome shortly after spinal cord injury. Profiling of the total and ribosome-bound RNA in injured and naïve spinal cords identify a substantial post-transcriptional regulation of gene expression. In particular, transcripts associated with nervous system development were downregulated in the total RNA-fraction while remaining stably loaded onto ribosomes. Interestingly, motif association analysis of post-transcriptionally regulated transcripts identified the cytoplasmic polyadenylation element (CPE) as enriched in a subset of these transcripts that was more resistant to injury-induced reduction at transcriptome level. Modulation of these transcripts by overexpression of the CPE binding protein, Cpeb1, in mouse and Drosophila CNS neurons promoted axonal regeneration following injury. Our study uncovers a global conserved post-transcriptional mechanism enhancing regeneration of injured CNS axons.