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Series GSE69800 Query DataSets for GSE69800
Status Public on Oct 01, 2015
Title Ribosome profiling analysis of GADD34 null cells
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Accumulation of misfolded proteins in the endoplasmic reticulum (ER) triggers the unfolded protein response (UPR), which results in the increased phosphorylation of the eukaryotic initiation factor, eIF2a, and widespread translational repression. Protein synthesis is subsequently restored following the stress-induced transcriptional upregulation of GADD34 (growth arrest and DNA damage transcript 34) protein, a regulator of an eIF2a phosphatase. Genome-wide ribosome foot-printing in WT and GADD34-/- MEFs established that GADD34 mRNA is translated in unstressed cells and identified numerous mRNAs, whose translation was dependent on GADD34 even in the absence of ER stress. Following UPR activation, temporal analyses showed that the translational profile in GADD34-/- MEFs was stalled, displaying a pattern that mirrors the early response to UPR in WT MEFs. Basal GADD34 expression is also required for de-repression of translation and displacement of ER-bound polysomes that occur in early UPR. Thus, the overall UPR response is delayed in the GADD34-/- MEFs, gradually recovering as CReP expression increased. These studies reveal a critical role for basal GADD34 in the propagation of UPR signals in MEFs and mice and suggest that delayed UPR signaling protects GADD34-/- mice from tunicamycin-induced renal toxicity.
Overall design Translational and transcriptional analysis mouse embryonic fibroblasts lacking GADD34 during ER stress
Contributor(s) Reid DW, Tay AL, Nicchitta CV, Shenolikar S
Citation(s) 27161320
Submission date Jun 11, 2015
Last update date May 15, 2019
Contact name David Reid
Organization name Duke University
Department Biochemistry
Lab Nicchitta
Street address 436 Nanaline Duke Bldg., Box 3709 DUMC
City Durham
State/province NC
ZIP/Postal code 27710
Country USA
Platforms (1)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
Samples (40)
GSM1709012 ER Ribosome profiling Untreated 1
GSM1709013 ER Ribosome profiling 0.5 h Tg 1
GSM1709014 ER Ribosome profiling 1 h Tg 1
BioProject PRJNA286792
SRA SRP059390

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Supplementary file Size Download File type/resource
GSE69800_gadd34-summary-expression.xlsx 4.2 Mb (ftp)(http) XLSX
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