RT Journal Article
SR Electronic
T1 ARGLU1 is a Glucocorticoid Receptor Coactivator and Splicing Modulator Important in Stress Hormone Signaling and Brain Development
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 069161
DO 10.1101/069161
A1 Lilia Magomedova
A1 Jens Tiefenbach
A1 Emma Zilberman
A1 Veronique Voisin
A1 Melanie Robitaille
A1 Serge Gueroussov
A1 Manuel Irimia
A1 Debashish Ray
A1 Rucha Patel
A1 ChangJiang Xu
A1 Pancharatnam Jeyasuria
A1 Gary D. Bader
A1 Timothy R. Hughes
A1 Henry Krause
A1 Benjamin J. Blencowe
A1 Stephane Angers
A1 Carolyn L. Cummins
YR 2016
UL http://biorxiv.org/content/early/2016/08/12/069161.abstract
AB 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.