The Long Noncoding RNA Pnky Regulates Neuronal Differentiation of Embryonic and Postnatal Neural Stem Cells

摘要

While thousands of long noncoding RNAs (lncRNAs)have been identified, few lncRNAs that control neuralstem cell (NSC) behavior are known. Here, we identifyPinky (Pnky) as a neural-specific lncRNA that regulatesneurogenesis from NSCs in the embryonicand postnatal brain. In postnatal NSCs, Pnky knockdownpotentiates neuronal lineage commitmentand expands the transit-amplifying cell population,increasing neuron production several-fold. Pnky isevolutionarily conserved and expressed in NSCsof the developing human brain. In the embryonicmouse cortex, Pnky knockdown increases neuronaldifferentiation and depletes the NSC population.Pnky interacts with the splicing regulator PTBP1,and PTBP1 knockdown also enhances neurogenesis.In NSCs, Pnky and PTBP1 regulate the expressionand alternative splicing of a core set of transcriptsthat relates to the cellular phenotype. Thesedata thus unveil Pnky as a conserved lncRNA thatinteracts with a key RNA processing factor and regulatesneurogenesis from embryonic and postnatalNSC populations.