Axonal Localization of Transgene mRNA in Mature PNS and CNS Neurons

Axonal mRNA transport is robust in cultured neurons but there has been limited evidence for this in vivo. We have used a genetic approach to test for in vivo axonal transport of reporter mRNAs. We show that beta-actin's 3'-UTR can drive axonal localization of GFP mRNA in mature DRG neurons, but mice with gamma-actin's 3'-UTR show no axonal GFP mRNA. Peripheral axotomy triggers transport of the beta-actin 3'-UTR containing transgene mRNA into axons. This GFP-3'-beta-actin mRNA accumulates in injured PNS axons before activation of the transgene promoter peaks in the DRG. Spinal cord injury also increases axonal GFP signals in mice carrying this transgene without any increase in transgene expression in the DRGs. These data show for the first time that the beta-actin 3'-UTR is sufficient for axonal localization in both PNS and CNS neurons in vivo.