When it comes to nerve damage, the mammalian peripheral nervous system (PNS) is arms and legs ahead of the central nervous system (CNS) in its ability to regenerate damaged neurons. While neuroscientists already knew that the PNS has an innate ability to express pro-regenerative transcription factors after injury, a new paper has the nerve to suggest that this phenomenon might be regulated by long non-coding RNA (lncRNA).
Using strand-specific sequencing of total RNA fractions, the lab of Igor Ulitsky (Weizmann Institute of Science, Israel) found that a unique set of genes are expressed in the dorsal root ganglia (DRG) of mice during recovery from a peripheral nerve injury. The DRG contains the cell bodies of peripheral sensory nerves, including the sciatic nerve, which the researchers injured as a model of regeneration in this study. Among the regeneration-related RNAs is the tissue-specific lncRNA that they named sciatic-injury-induced lncRNA 1 or Silc1 for short.
Their cascade of follow-up experiments found that:
- Silc1 silencing via RNAi in cultured DRG neurons reduces the expression of Sox11, a pro-regenerative factor that resides on the same chromosome
- Neurons without Silc1 have impaired axonal growth compared to control neurons, but this can be rescued by lentivirus mediated over-expression of Sox11
- Silc1-/- knockout mice show normal levels of Sox11 expression during development and in adult DRG neurons, except after sciatic nerve injury where knockout mice have less Sox11 than their control littermates
- Silc1-/- knockout mice take longer to recover from nerve injury, and their damaged DRGs have impaired gene expression profiles
- The Silc1gene contains enhancer sequences that promote Sox11 expression during development, independently of its function as a lncRNA in the DRG after nerve injury
Even though Silc1 is necessary for proper axon regeneration, adding extra Silc1 to damaged neurons won’t cut it; the lncRNA only promotes the expression of the Sox11 gene of the same allele, which suggests that a three-dimensional chromatin structure is likely involved. Although it’s still not clear how the two genes interact, it’s an exciting step towards understanding how nerve regeneration is regulated.