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PXD012555

PXD012555 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleBioID Assay of BirA*-hARGLU1 or BirA*-hGR in Flp-In T-Rex 293 cells
DescriptionARGLU1 is a Transcriptional Coactivator and Splicing Regulator Important for Stress Hormone Signaling and Development Stress hormones bind and activate the glucocorticoid receptor (GR) in many tissues including the brain. We identified arginine and glutamate rich 1 (ARGLU1) in a screen for new modulators of glucocorticoid signaling in the CNS. Biochemical studies show that the glutamate rich C-terminus of ARGLU1 coactivates multiple nuclear receptors including the glucocorticoid receptor (GR) and the arginine rich N-terminus interacts with splicing factors and binds to RNA. RNA-seq of neuronal cells depleted of ARGLU1 revealed significant changes in the expression and alternative splicing of distinct genes involved in neurogenesis. Loss of ARGLU1 is embryonic lethal in mice, and knockdown in zebrafish causes neurodevelopmental and heart defects. Treatment with dexamethasone, a GR activator, also induces changes in the pattern of alternatively spliced genes, many of which were lost when ARGLU1 was absent. Importantly, the genes found to be alternatively spliced in response to glucocorticoid treatment were distinct from those under transcriptional control by GR, suggesting an additional mechanism of glucocorticoid action is present in neuronal cells. Our results thus show that ARGLU1 is a novel factor for embryonic development that modulates basal transcription and alternative splicing in neuronal cells with consequences for glucocorticoid signaling.
HostingRepositoryPRIDE
AnnounceDate2019-03-06
AnnouncementXMLSubmission_2019-03-06_02:12:36.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterMichael Saikali
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListbiotinylated residue
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02019-01-29 03:38:32ID requested
12019-02-15 06:59:29announced
22019-03-06 02:12:37announcedUpdated project metadata.
Publication List
Magomedova L, Tiefenbach J, Zilberman E, Le Billan F, Voisin V, Saikali M, Boivin V, Robitaille M, Gueroussov S, Irimia M, Ray D, Patel R, Xu C, Jeyasuria P, Bader GD, Hughes TR, Morris QD, Scott MS, Krause H, Angers S, Blencowe BJ, Cummins CL, ARGLU1 is a transcriptional coactivator and splicing regulator important for stress hormone signaling and development. Nucleic Acids Res, 47(6):2856-2870(2019) [pubmed]
Keyword List
curator keyword: Biological
submitter keyword: ARGLU1, GR, NR3C1, Splicing
Contact List
Carolyn Cummins
contact affiliationDepartment of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto
contact emailcarolyn.cummins@utoronto.ca
lab head
Michael Saikali
contact affiliationUniversity of Toronto
contact emailmichael.saikali@mail.utoronto.ca
dataset submitter
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Dataset FTP location
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