Mehdi Amiri, Stephen J Kiniry, Anthony P Possemato, Niaz Mahmood, Tayebeh Basiri, Catherine R Dufour, Negar Tabatabaei, Qiyun Deng, Michael A Bellucci, Keerthana Harwalkar, Matthew P Stokes, Vincent Giguère, Randal J Kaufman, Yojiro Yamanaka, Pavel V Baranov, Soroush Tahmasebi, Nahum Sonenberg
The integrated stress response (ISR) is critical for cell survival under stress. In response to diverse environmental cues, eIF2α 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 (eIF2α+/+ ) and phosphorylation-deficient mutant eIF2α (eIF2αA/A ) mouse ESCs (mESCs) to investigate phosphorylated (p)-eIF2α-dependent translational control of naive pluripotency...
December 28, 2023: Cell Reports