Regulation of Neuroregeneration by Long Noncoding RNAs

In mammals, neurons in the peripheral nervous system (PNS) have regenerative capacity following injury, but it is generally absent in the CNS. This difference is attributed, at least in part, to the intrinsic ability of PNS neurons to activate a unique regenerative transcriptional program following injury. Here, we profiled gene expression following sciatic nerve crush in mice and identified long noncoding RNAs (lncRNAs) that act in the regenerating neurons and which are typically not expressed in other contexts. We show that two of these lncRNAs regulate the extent of neuronal outgrowth. We then focus on one of these, Silc1, and show that it regulates neuroregeneration in cultured cells and in vivo, through cis-acting activation of the transcription factor Sox11. [Display omitted] •Dozens of long noncoding RNAs (lncRNAs) are induced in the DRGs upon sciatic injury•Depletion of two such lncRNAs leads to impaired neurite outgrowth•Silc1 lncRNA acts by activating in cis the expression of Sox11 transcription factor•Loss of Silc1 in mice leads to a delayed regeneration following sciatic nerve crush Ben-Tov Perry et al. identified long noncoding RNAs expressed during neuroregeneration. Depletion of Silc1 and Norris1 leads to impaired neurite outgrowth in vitro, and loss of Silc1 in vivo leads to delayed regeneration. Silc1 activates in cis the expression of Sox11, located ∼200 kb away on the same chromosome.