Reid et al. 2015 (PRJNA286792)
General Details
| Title | Ribosome profiling analysis of GADD34 null cells |
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| Organism | |
| Number of Samples | 20 |
| Release Date | 2015/06/11 00:00 |
| Sequencing Types | |
| Protocol Details |
Study Links
| GWIPS-viz | Trips-Viz |
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Repository Details
| SRA | SRP059390 |
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| ENA | SRP059390 |
| GEO | GSE69800 |
| BioProject | PRJNA286792 |
Publication
| Title | |
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| 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) | ||
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| SRR2060674 | PRJNA286792 | Mus musculus | Fibroblast | Ribo-Seq | Cycloheximide |  |
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| SRR2060675 | PRJNA286792 | Mus musculus | Fibroblast | Ribo-Seq | Cycloheximide | |
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| SRR2060676 | PRJNA286792 | Mus musculus | Fibroblast | Ribo-Seq | Cycloheximide | |
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| SRR2060677 | PRJNA286792 | Mus musculus | Fibroblast | Ribo-Seq | Cycloheximide | |
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| SRR2060678 | PRJNA286792 | Mus musculus | Fibroblast | Ribo-Seq | Cycloheximide | |
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| SRR2060679 | PRJNA286792 | Mus musculus | Fibroblast | Ribo-Seq | Cycloheximide | |
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| SRR2060680 | PRJNA286792 | Mus musculus | Fibroblast | Ribo-Seq | Cycloheximide | |
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| SRR2060681 | PRJNA286792 | Mus musculus | Fibroblast | Ribo-Seq | Cycloheximide | |
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| SRR2060682 | PRJNA286792 | Mus musculus | Fibroblast | Ribo-Seq | Cycloheximide | |
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| SRR2060683 | PRJNA286792 | Mus musculus | Fibroblast | Ribo-Seq | Cycloheximide | |
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| SRR2060684 | PRJNA286792 | Mus musculus | Fibroblast | Ribo-Seq | Cycloheximide | |
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| SRR2060685 | PRJNA286792 | Mus musculus | Fibroblast | Ribo-Seq | Cycloheximide | |
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| SRR2060686 | PRJNA286792 | Mus musculus | Fibroblast | Ribo-Seq | Cycloheximide | |
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| SRR2060687 | PRJNA286792 | Mus musculus | Fibroblast | Ribo-Seq | Cycloheximide | |
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| SRR2060688 | PRJNA286792 | Mus musculus | Fibroblast | Ribo-Seq | Cycloheximide | |
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| SRR2060689 | PRJNA286792 | Mus musculus | Fibroblast | Ribo-Seq | Cycloheximide | |
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| SRR2060690 | PRJNA286792 | Mus musculus | Fibroblast | Ribo-Seq | Cycloheximide | |
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| SRR2060691 | PRJNA286792 | Mus musculus | Fibroblast | Ribo-Seq | Cycloheximide | |
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| SRR2060692 | PRJNA286792 | Mus musculus | Fibroblast | Ribo-Seq | Cycloheximide | |
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| SRR2060693 | PRJNA286792 | Mus musculus | Fibroblast | Ribo-Seq | Cycloheximide | |
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| 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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