Reid et al. 2015 (PRJNA286792)

General Details

Title Ribosome profiling analysis of GADD34 null cells
Organism
Number of Samples 20
Release Date 2015/06/11 00:00
Sequencing Types
Protocol Details

Study Links

Repository Details

SRA SRP059390
ENA SRP059390
GEO
BioProject PRJNA286792

Publication

Title
Authors Reid DW,Tay AS,Sundaram JR,Lee IC,Chen Q,George SE,Nicchitta CV,Shenolikar S
Journal Molecular and cellular biology
Publication Date 2016 Jul 1
Abstract Phosphorylation of eukaryotic initiation factor 2α (eIF2α) controls transcriptome-wide changes in mRNA translation in stressed cells. While phosphorylated eIF2α (P-eIF2α) attenuates global protein synthesis, mRNAs encoding stress proteins are more efficiently translated. Two eIF2α phosphatases, containing GADD34 and CReP, catalyze P-eIF2α dephosphorylation. The current view of GADD34, whose transcription is stress induced, is that it functions in a feedback loop to resolve cell stress. In contrast, CReP, which is constitutively expressed, controls basal P-eIF2α levels in unstressed cells. Our studies show that GADD34 drives substantial changes in mRNA translation in unstressed cells, particularly targeting the secretome. Following activation of the unfolded protein response (UPR), rapid translation of GADD34 mRNA occurs and GADD34 is essential for UPR progression. In the absence of GADD34, eIF2α phosphorylation is persistently enhanced and the UPR translational program is significantly attenuated. This 'stalled' UPR is relieved by the subsequent activation of compensatory mechanisms that include AKT-mediated suppression of PKR-like kinase (PERK) and increased expression of CReP mRNA, partially restoring protein synthesis. Our studies highlight the coordinate regulation of UPR by the GADD34- and CReP-containing eIF2α phosphatases to control cell viability. Copyright © 2016, American Society for Microbiology. All Rights Reserved.
PMC PMC4911741
PMID 27161320
DOI
Run Accession Study Accession Scientific Name Cell Line Library Type Treatment GWIPS-viz Trips-Viz Reads BAM BigWig (F) BigWig (R)
SRR2060674 PRJNA286792 Mus musculus embryonic fibroblast Ribo-Seq untreated
SRR2060675 PRJNA286792 Mus musculus embryonic fibroblast Ribo-Seq
SRR2060676 PRJNA286792 Mus musculus embryonic fibroblast Ribo-Seq
SRR2060677 PRJNA286792 Mus musculus embryonic fibroblast Ribo-Seq
SRR2060678 PRJNA286792 Mus musculus embryonic fibroblast Ribo-Seq
SRR2060679 PRJNA286792 Mus musculus embryonic fibroblast Ribo-Seq untreated
SRR2060680 PRJNA286792 Mus musculus embryonic fibroblast Ribo-Seq
SRR2060681 PRJNA286792 Mus musculus embryonic fibroblast Ribo-Seq
SRR2060682 PRJNA286792 Mus musculus embryonic fibroblast Ribo-Seq
SRR2060683 PRJNA286792 Mus musculus embryonic fibroblast Ribo-Seq
SRR2060684 PRJNA286792 Mus musculus embryonic fibroblast Ribo-Seq untreated
SRR2060685 PRJNA286792 Mus musculus embryonic fibroblast Ribo-Seq
SRR2060686 PRJNA286792 Mus musculus embryonic fibroblast Ribo-Seq
SRR2060687 PRJNA286792 Mus musculus embryonic fibroblast Ribo-Seq
SRR2060688 PRJNA286792 Mus musculus embryonic fibroblast Ribo-Seq
SRR2060689 PRJNA286792 Mus musculus embryonic fibroblast Ribo-Seq untreated
SRR2060690 PRJNA286792 Mus musculus embryonic fibroblast Ribo-Seq
SRR2060691 PRJNA286792 Mus musculus embryonic fibroblast Ribo-Seq
SRR2060692 PRJNA286792 Mus musculus embryonic fibroblast Ribo-Seq
SRR2060693 PRJNA286792 Mus musculus embryonic fibroblast Ribo-Seq
Run Accession Study Accession Scientific Name Cell Line Library Type Treatment GWIPS-viz Trips-Viz Reads BAM BigWig (F) BigWig (R)

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