Identification of neural stem cell differentiation repressor complex Pnky-PTBP1

Splicing increases immensely the complexity of gene products expressed in the cell. The precise regulation of splicing is critical for the development, homeostasis, and function of all tissues in the body, including those comprising the neural system. Ramos et al. recently identified Pnky as a long noncoding RNA expressed selectively in neural tissues that was implicated in the transition of neural stem cells (NSCs) to mature neurons. Pnky actions appeared to be mediated by its interaction with the splicing factor and RNA-binding protein (RBP) polypyrimidine tract-binding protein (PTBP1), as silencing either Pnky or PTBP1 modulated in similar ways the patterns of spliced and expressed mRNAs in the cell. Strikingly, lowering the expression levels of Pnky or PTBP1 in NSCs actually enhanced neurogenesis, suggesting that the Pnky-PTBP1 complex elicited a splicing program of suppression of neurogenesis. With rapid progress in the design and delivery of RNA-based therapies, interventions to reduce Pnky levels may prove beneficial towards enhancing neurogenesis in disease states characterized by aberrant neuronal loss.