Pantr2, a trans-acting lncRNA, modulates the differentiation potential of neural progenitors in vivo

Kavli Affiliate: Seth Blackshaw, Loyal Goff

| Authors: Jonathan J Augustin, Saki Takayangi, Thanh Hoang, Briana Winer, Seth Blackshaw and Loyal A Goff

| Summary:

Abstract Ablation of the long non-coding RNA (lncRNA) Pantr2 re- sults in microcephaly in a knockout murine model of cor- ticogenesis, however, the precise mechanisms used are un- known. We present evidence that Pantr2 is a trans-acting lncRNA that regulates gene expression and chromatin ac- cessibility both in vivo and in vitro. We demonstrate that ec- topic expression of Pantr2 in a neuroblastoma cell line alters gene expression under differentiating conditions, and that both loss and gain of function of Pantr2 results in changes to cell-cycle dynamics. We show that expression of both the transcription factor Nfix and the cell cycle regulator Rgcc are negatively regulated by Pantr2. Using RNA binding pro- tein motif analysis and existing CLIP-seq data, we annotate potential HuR and QKI binding sites on Pantr2, and demon- strate that HuR does not directly bind Pantr2 using RNA immunoprecipitation assay. Finally, using Gene Ontology enrichment analysis, we identify disruption of both Notch and Wnt signaling following loss of Pantr2 expression, indi- cating potential Pantr2-dependent regulation of these path- ways. Competing Interest Statement The authors have declared no competing interest.

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