1. The Long Noncoding RNA Pnky Is a Trans-acting Regulator of Cortical Development In Vivo.
- Author
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Andersen RE, Hong SJ, Lim JJ, Cui M, Harpur BA, Hwang E, Delgado RN, Ramos AD, Liu SJ, Blencowe BJ, and Lim DA
- Subjects
- Animals, Brain metabolism, Cerebral Cortex metabolism, Female, Interneurons metabolism, Male, Mice, Mice, Inbred C57BL, Nerve Tissue Proteins genetics, Neurogenesis genetics, Neurons metabolism, POU Domain Factors genetics, RNA, Long Noncoding metabolism, Trans-Activators genetics, Trans-Activators metabolism, Transcription Factors metabolism, Cerebral Cortex embryology, Neural Stem Cells metabolism, RNA, Long Noncoding genetics
- 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 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., (Published by Elsevier Inc.)
- Published
- 2019
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