1. The Long Noncoding RNA Pnky Is a Trans-acting Regulator of Cortical Development In Vivo
- Author
-
Andersen, Rebecca E, Hong, Sung Jun, Lim, Justin J, Cui, Miao, Harpur, Brock A, Hwang, Elizabeth, Delgado, Ryan N, Ramos, Alexander D, Liu, Siyuan John, Blencowe, Benjamin J, and Lim, Daniel A
- Subjects
Male ,lncRNA knockout mouse ,Neurogenesis ,1.1 Normal biological development and functioning ,Nerve Tissue Proteins ,Inbred C57BL ,trans-acting lncRNA ,Medical and Health Sciences ,Mice ,lncRNA ,Neural Stem Cells ,Interneurons ,Underpinning research ,Genetics ,Animals ,long noncoding RNA ,Cerebral Cortex ,Neurons ,neurodevelopment ,Neurosciences ,Brain ,NSCs ,Biological Sciences ,Stem Cell Research ,POU Domain Factors ,Trans-Activators ,RNA ,Female ,Long Noncoding ,Stem Cell Research - Nonembryonic - Non-Human ,BAC transgenic rescue ,Transcription Factors ,Developmental Biology - Abstract
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 invivo, 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 invivo. Thus, despite being transcribed divergently from a key developmental transcription factor, the lncRNA Pnky regulates development in trans.
- Published
- 2019