Alternative RNA splicing associated with axon regeneration after rat peripheral nerve injury.

The intrinsic axon regeneration capacity is crucial for peripheral nerve regeneration after injury. Identifying key molecules involved in this process makes great contribution to the investigation of peripheral nerve injury repair. Alternative splicing (AS) is an important regulation mode of eukaryotic gene expression, which has been widely studied both in physiological and pathological processes. However, less is known about the role of AS in peripheral nerve regeneration. In this work, to identify the AS events associated with axon regeneration capacity, we analyzed the AS events during sciatic nerve injury repair by RNA sequencing (RNA-Seq) and replicate multivariate analysis of transcript splicing (rMATS). The differential AS events were underwent gene ontology enrichment and pathway analyses. Moreover, we identified a significantly increased AS event of neuronal cell adhesion molecule Nrcam (Nrcam-S), and demonstrated down-regulation of Nrcam-S by specific siRNAs inhibited axon regeneration of Dorsal Root Ganglion (DRG) neurons after sciatic nerve injury in vitro and in vivo. Additionally, we found expression levels of RNA binding proteins (RBPs) CUGBP Elav-like family member 3 (CELF3) and RNA binding protein fox-1 homolog 2 (Rbfox2) were markedly increased after sciatic nerve injury. Our data may serve as a resource useful for further understanding how AS contributes to molecular regulations in DRG during sciatic nerve regeneration.