TRBP maintains mammalian embryonic neural stem cell properties by enhancing the Notch signaling pathway as a novel transcriptional coactivator

• DOI: 10.1242/dev.139493
• Publication Date: 2017-02-08T01:25:39Z
• Authors: Sung-Hyun Byun; Juwan Kim; Dasol Han; Mookwang Kwon; Jae Youl Cho; Hui Xuan Ng; Samuel J. Pleasure; Keejung Yoon
• Keywords: Cell Nucleus; Central Nervous System; Transcriptional Activation; 0301 basic medicine; Receptors, Notch; Brain; Gene Expression Regulation, Developmental; RNA-Binding Proteins; 3. Good health; Mice; MicroRNAs; 03 medical and health sciences; HEK293 Cells; Neural Stem Cells; Immunoglobulin J Recombination Signal Sequence-Binding Protein; Animals; Humans; Promoter Regions, Genetic; Embryonic Stem Cells; In Situ Hybridization; Glutathione Transferase; Signal Transduction

Transactivation response element RNA-binding protein (TRBP) is known to play important roles in human immunodeficiency virus (HIV) replication and microRNA biogenesis. However, recent studies implicate TRBP in a variety of biological processes as a mediator for cross-talk between signal transduction pathways. Here, we provide the first evidence that TRBP is required for efficient neurosphere formation, and expression of neural stem cell markers and Notch target genes in primary neural progenitor cells in vitro. Consistent with this, introduction of TRBP into the mouse embryonic brain in utero increased the fraction of cells expressing Sox2 in the ventricular zone (VZ). We also show TRBP physically interacts with the Notch transcriptional coactivation complex through C promoter binding factor 1 (CBF1) and strengthens the association between the Notch intracellular domain (NICD) and CBF1, resulting in increased NICD recruitment to the promoter region of a Notch target gene. Our data indicate that TRBP is a novel transcriptional coactivator of the Notch signaling pathway playing an important role in neural stem cell regulation during mammalian brain development.