TY - JOUR T1 - ARGLU1 is a Glucocorticoid Receptor Coactivator and Splicing Modulator Important in Stress Hormone Signaling and Brain Development JF - bioRxiv DO - 10.1101/069161 SP - 069161 AU - Lilia Magomedova AU - Jens Tiefenbach AU - Emma Zilberman AU - Veronique Voisin AU - Melanie Robitaille AU - Serge Gueroussov AU - Manuel Irimia AU - Debashish Ray AU - Rucha Patel AU - ChangJiang Xu AU - Pancharatnam Jeyasuria AU - Gary D. Bader AU - Timothy R. Hughes AU - Henry Krause AU - Benjamin J. Blencowe AU - Stephane Angers AU - Carolyn L. Cummins Y1 - 2016/01/01 UR - http://biorxiv.org/content/early/2016/08/12/069161.abstract N2 - Prolonged exposure to glucocorticoid stress hormones precipitates mood and cognitive disorders. We identified arginine and glutamate rich 1 (ARGLU1) in a screen for new modulators of glucocorticoid signaling in the CNS. Biochemical studies found that the glutamate rich C-terminus coactivates the glucocorticoid receptor (GR) and the arginine rich N-terminus interacts with splicing factors and RNA. RNA-seq of neuronal cells ±siARGLU1found significant changes in the expression and alternative splicing of distinct genes involved in neurogenesis. Loss of ARGLU1 was embryonic lethal in mice, and knockdown in zebrafish caused neurodevelopmental and heart defects. Treatment with dexamethasone, a GR activator, also induced changes in the pattern of alternatively spliced genes, highlighting an underappreciated global mechanism of glucocorticoid action in neuronal cells. Thus, in addition to its basal role, ARGLU1 links glucocorticoid-mediated transcription and alternative splicing in neural cells, providing new avenues from which to investigate the molecular underpinnings of cognitive stress disorders. ER -