TRBP maintains mammalian embryonic neural stem cell properties by acting as a novel transcriptional coactivator of the Notch signaling pathway.
Transactivation response element RNA-binding protein (TRBP; TARBP2) 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 of cross-talk between signal transduction pathways. Here, we provide the first evidence that TRBP is required for efficient neurosphere formation and for the expression of neural stem cell markers and Notch target genes in primary neural progenitor cellsin vitroConsistent with this, introduction of TRBP into the mouse embryonic brainin uteroincreased the fraction of cells expressing Sox2 in the ventricular zone. We also show that TRBP physically interacts with the Notch transcriptional coactivation complex through C promoter-binding factor 1 (CBF1; RBPJ) 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.
Department of Genetic Engineering, College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon, Gyeonggi-do 16419, South Korea.
Sung-Hyun
SH
Byun
Department of Genetic Engineering, College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon, Gyeonggi-do 16419, South Korea.
Juwan
J
Kim
Department of Genetic Engineering, College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon, Gyeonggi-do 16419, South Korea.
Dasol
D
Han
Department of Genetic Engineering, College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon, Gyeonggi-do 16419, South Korea.
Mookwang
M
Kwon
Department of Genetic Engineering, College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon, Gyeonggi-do 16419, South Korea.
Jae Youl
JY
Cho
Department of Neurology, University of California San Francisco, San Francisco, CA 94158, USA.
Hui Xuan
HX
Ng
Department of Neurology, University of California San Francisco, San Francisco, CA 94158, USA.
Samuel J
SJ
Pleasure
Department of Genetic Engineering, College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon, Gyeonggi-do 16419, South Korea keejung@skku.edu.
Keejung
0000-0002-2361-9039
K
Yoon
D000818:Animals; D001921:Brain / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D002490:Central Nervous System / Q000196:embryology; D053595:Embryonic Stem Cells / Q000166:cytology; D018507:Gene Expression Regulation, Developmental; D005982:Glutathione Transferase / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein / Q000378:metabolism; D017403:In Situ Hybridization; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism; D058953:Neural Stem Cells / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D016601:RNA-Binding Proteins / Q000378:metabolism*; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction; D015533:Transcriptional Activation; D000099253:Trans-Activation Responsive RNA-Binding Protein
D005982:Glutathione Transferase; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; D035683:MicroRNAs; D016601:RNA-Binding Proteins; D051880:Receptors, Notch; D000099253:Trans-Activation Responsive RNA-Binding Protein; C497570:RBPJ protein, human
Central nervous system development; Embryonic neural stem cells; Notch; TRBP; Transcriptional activation