| First Author | Amiri M | Year | 2024 |
| Journal | Cell Rep | Volume | 43 |
| Issue | 1 | Pages | 113615 |
| PubMed ID | 38159280 | Mgi Jnum | J:346137 |
| Mgi Id | MGI:7613998 | Doi | 10.1016/j.celrep.2023.113615 |
| Citation | Amiri M, et al. (2024) Impact of eIF2alpha phosphorylation on the translational landscape of mouse embryonic stem cells. Cell Rep 43(1):113615 |
| abstractText | The integrated stress response (ISR) is critical for cell survival under stress. In response to diverse environmental cues, eIF2alpha becomes phosphorylated, engendering a dramatic change in mRNA translation. The activation of ISR plays a pivotal role in the early embryogenesis, but the eIF2-dependent translational landscape in pluripotent embryonic stem cells (ESCs) is largely unexplored. We employ a multi-omics approach consisting of ribosome profiling, proteomics, and metabolomics in wild-type (eIF2alpha(+/+)) and phosphorylation-deficient mutant eIF2alpha (eIF2alpha(A/A)) mouse ESCs (mESCs) to investigate phosphorylated (p)-eIF2alpha-dependent translational control of naive pluripotency. We show a transient increase in p-eIF2alpha in the naive epiblast layer of E4.5 embryos. Absence of eIF2alpha phosphorylation engenders an exit from naive pluripotency following 2i (two chemical inhibitors of MEK1/2 and GSK3alpha/beta) withdrawal. p-eIF2alpha controls translation of mRNAs encoding proteins that govern pluripotency, chromatin organization, and glutathione synthesis. Thus, p-eIF2alpha acts as a key regulator of the naive pluripotency gene regulatory network. |
