The Long Noncoding RNA Pnky Is a Trans-acting Regulator of Cortical Development In Vivo

While it is now appreciated that certain long noncoding RNAs (lncRNAs) have important functions in cell biology, relatively few have been shown to regulate development in vivo, particularly with genetic strategies that establish cis versus trans mechanisms. Pnky is a nuclear-enriched lncRNA that is transcribed divergently from the neighboring proneural transcription factor Pou3f2. Here, we show that conditional deletion of Pnky from the developing cortex regulates the production of projection neurons from neural stem cells (NSCs) in a cell-autonomous manner, altering postnatal cortical lamination. Surprisingly, Pou3f2 expression is not disrupted by deletion of the entire Pnky gene. Moreover, expression of Pnky from a BAC transgene rescues the differential gene expression and increased neurogenesis of Pnky-knockout NSCs, as well as the developmental phenotypes of Pnky-deletion in vivo. Thus, despite being transcribed divergently from a key developmental transcription factor, the lncRNA Pnky regulates development in trans. [Display omitted] •Pnky is a long noncoding RNA that regulates cortical development in vivo•Pnky acts cell-autonomously to affect neuron production in the developing cortex•Despite its divergent configuration with Pou3f2, Pnky does not regulate Pou3f2•BAC transgenic rescue demonstrates that Pnky functions in trans Long noncoding RNAs (lncRNAs) can play important roles in cells, but the in vivo functions of most lncRNAs remain unclear. Andersen et al. find that the lncRNA Pnky regulates neuron production in the developing mouse cortex in a cell-autonomous manner and further demonstrate that Pnky functions in trans.