دورية أكاديمية
Impact of eIF2α phosphorylation on the translational landscape of mouse embryonic stem cells.
العنوان: | Impact of eIF2α phosphorylation on the translational landscape of mouse embryonic stem cells. |
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المؤلفون: | Amiri M; Department of Biochemistry, McGill University, Montreal, QC H3A 1A3, Canada; Rosalind and Morris Goodman Cancer Institute, McGill University, Montreal, QC H3A 1A3, Canada., Kiniry SJ; School of Biochemistry and Cell Biology, University College Cork, T12 XF62 Cork, Ireland., Possemato AP; Cell Signaling Technology, Inc., 3 Trask Lane, Danvers, MA 01923, USA., Mahmood N; Department of Biochemistry, McGill University, Montreal, QC H3A 1A3, Canada; Rosalind and Morris Goodman Cancer Institute, McGill University, Montreal, QC H3A 1A3, Canada., Basiri T; Department of Biochemistry, McGill University, Montreal, QC H3A 1A3, Canada; Rosalind and Morris Goodman Cancer Institute, McGill University, Montreal, QC H3A 1A3, Canada., Dufour CR; Rosalind and Morris Goodman Cancer Institute, McGill University, Montreal, QC H3A 1A3, Canada., Tabatabaei N; Department of Pharmacology and Regenerative Medicine, University of Illinois College of Medicine, Chicago, IL 60612, USA., Deng Q; Department of Biochemistry, McGill University, Montreal, QC H3A 1A3, Canada; Rosalind and Morris Goodman Cancer Institute, McGill University, Montreal, QC H3A 1A3, Canada., Bellucci MA; Department of Biochemistry, McGill University, Montreal, QC H3A 1A3, Canada; Rosalind and Morris Goodman Cancer Institute, McGill University, Montreal, QC H3A 1A3, Canada., Harwalkar K; Rosalind and Morris Goodman Cancer Institute, McGill University, Montreal, QC H3A 1A3, Canada; Department of Human Genetics, McGill University, Montreal, QC H3A 0C7, Canada., Stokes MP; Cell Signaling Technology, Inc., 3 Trask Lane, Danvers, MA 01923, USA., Giguère V; Department of Biochemistry, McGill University, Montreal, QC H3A 1A3, Canada; Rosalind and Morris Goodman Cancer Institute, McGill University, Montreal, QC H3A 1A3, Canada., Kaufman RJ; Degenerative Diseases Program, Center for Genetic Disorders and Aging Research, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA., Yamanaka Y; Rosalind and Morris Goodman Cancer Institute, McGill University, Montreal, QC H3A 1A3, Canada; Department of Human Genetics, McGill University, Montreal, QC H3A 0C7, Canada., Baranov PV; School of Biochemistry and Cell Biology, University College Cork, T12 XF62 Cork, Ireland., Tahmasebi S; Department of Pharmacology and Regenerative Medicine, University of Illinois College of Medicine, Chicago, IL 60612, USA. Electronic address: sorousht@uic.edu., Sonenberg N; Department of Biochemistry, McGill University, Montreal, QC H3A 1A3, Canada; Rosalind and Morris Goodman Cancer Institute, McGill University, Montreal, QC H3A 1A3, Canada. Electronic address: nahum.sonenberg@mcgill.ca. |
المصدر: | Cell reports [Cell Rep] 2024 Jan 23; Vol. 43 (1), pp. 113615. Date of Electronic Publication: 2023 Dec 29. |
نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't; Research Support, N.I.H., Extramural |
اللغة: | English |
بيانات الدورية: | Publisher: Cell Press Country of Publication: United States NLM ID: 101573691 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2211-1247 (Electronic) NLM ISO Abbreviation: Cell Rep Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: [Cambridge, MA] : Cell Press, c 2012- |
مواضيع طبية MeSH: | Mouse Embryonic Stem Cells*/metabolism , Pluripotent Stem Cells*/metabolism, Animals ; Mice ; Embryonic Stem Cells/metabolism ; Phosphorylation ; RNA, Messenger/metabolism ; Eukaryotic Initiation Factor-2/metabolism |
مستخلص: | 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 (eIF2α A/A ) mouse ESCs (mESCs) to investigate phosphorylated (p)-eIF2α-dependent translational control of naive pluripotency. We show a transient increase in p-eIF2α in the naive epiblast layer of E4.5 embryos. Absence of eIF2α phosphorylation engenders an exit from naive pluripotency following 2i (two chemical inhibitors of MEK1/2 and GSK3α/β) withdrawal. p-eIF2α controls translation of mRNAs encoding proteins that govern pluripotency, chromatin organization, and glutathione synthesis. Thus, p-eIF2α acts as a key regulator of the naive pluripotency gene regulatory network. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.) |
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معلومات مُعتمدة: | P01 HL160472 United States HL NHLBI NIH HHS; R01 CA198103 United States CA NCI NIH HHS; R01 DK113171 United States DK NIDDK NIH HHS; R01 HL163806 United States HL NHLBI NIH HHS |
فهرسة مساهمة: | Keywords: Stem cell research; embryonic stem cells; p-eIF2α; pluripotency; ribosome profiling; translational control |
المشرفين على المادة: | 0 (RNA, Messenger) 0 (Eukaryotic Initiation Factor-2) |
تواريخ الأحداث: | Date Created: 20231230 Date Completed: 20240205 Latest Revision: 20240327 |
رمز التحديث: | 20240327 |
مُعرف محوري في PubMed: | PMC10962698 |
DOI: | 10.1016/j.celrep.2023.113615 |
PMID: | 38159280 |
قاعدة البيانات: | MEDLINE |
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