PMID- 36638791 OWN - NLM STAT- MEDLINE DCOM- 20230217 LR - 20240428 IS - 2213-6711 (Electronic) IS - 2213-6711 (Linking) VI - 18 IP - 2 DP - 2023 Feb 14 TI - Ribosomal proteins regulate 2-cell-stage transcriptome in mouse embryonic stem cells. PG - 463-474 LID - S2213-6711(22)00596-3 [pii] LID - 10.1016/j.stemcr.2022.12.007 [doi] AB - A rare sub-population of mouse embryonic stem cells (mESCs), the 2-cell-like cell, is defined by the expression of MERVL and 2-cell-stage-specific transcript (2C transcript). Here, we report that the ribosomal proteins (RPs) RPL14, RPL18, and RPL23 maintain the identity of mESCs and regulate the expression of 2C transcripts. Disregulation of the RPs induces DUX-dependent expression of 2C transcripts and alters the chromatin landscape. Mechanically, knockdown (KD) of RPs triggers the binding of RPL11 to MDM2, an interaction known to prevent P53 protein degradation. Increased P53 protein upon RP KD further activates its downstream pathways, including DUX. Our study delineates the critical roles of RPs in 2C transcript activation, ascribing a novel function to these essential proteins. CI - Copyright (c) 2022 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Yi, Yao AU - Yi Y AD - Cell Fate Engineering and Therapeutics Laboratory, Division of Cell Biology and Therapies, Institute of Molecular and Cell Biology, A( *)STAR, Singapore 138673, Singapore; Department of Biological Sciences, National University of Singapore, Singapore 117558, Singapore. FAU - Zeng, Yingying AU - Zeng Y AD - Cell Fate Engineering and Therapeutics Laboratory, Division of Cell Biology and Therapies, Institute of Molecular and Cell Biology, A( *)STAR, Singapore 138673, Singapore; School of Biological Sciences, Nanyang Technological University, Singapore 637551, Singapore. FAU - Sam, Tsz Wing AU - Sam TW AD - Cell Fate Engineering and Therapeutics Laboratory, Division of Cell Biology and Therapies, Institute of Molecular and Cell Biology, A( *)STAR, Singapore 138673, Singapore; Department of Physiology, Healthy Longevity Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117593, Singapore. FAU - Hamashima, Kiyofumi AU - Hamashima K AD - Cell Fate Engineering and Therapeutics Laboratory, Division of Cell Biology and Therapies, Institute of Molecular and Cell Biology, A( *)STAR, Singapore 138673, Singapore. FAU - Tan, Rachel Jun Rou AU - Tan RJR AD - Cell Fate Engineering and Therapeutics Laboratory, Division of Cell Biology and Therapies, Institute of Molecular and Cell Biology, A( *)STAR, Singapore 138673, Singapore. FAU - Warrier, Tushar AU - Warrier T AD - Cell Fate Engineering and Therapeutics Laboratory, Division of Cell Biology and Therapies, Institute of Molecular and Cell Biology, A( *)STAR, Singapore 138673, Singapore. FAU - Phua, Jun Xiang AU - Phua JX AD - Cell Fate Engineering and Therapeutics Laboratory, Division of Cell Biology and Therapies, Institute of Molecular and Cell Biology, A( *)STAR, Singapore 138673, Singapore. FAU - Taneja, Reshma AU - Taneja R AD - Department of Physiology, Healthy Longevity Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117593, Singapore. FAU - Liou, Yih-Cherng AU - Liou YC AD - Department of Biological Sciences, National University of Singapore, Singapore 117558, Singapore. FAU - Li, Hu AU - Li H AD - Center for Individualized Medicine, Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN 55905, USA. FAU - Xu, Jian AU - Xu J AD - Department of Plant Systems Physiology, Institute for Water and Wetland Research, Radboud University, Heyendaalseweg 135, 6525 AJ Nijmegen, the Netherlands; Department of Biological Sciences and Centre for BioImaging Sciences, National University of Singapore, Singapore 117543, Singapore; Joint Center for Single Cell Biology, Shandong Agricultural University, Tai'an, Shandong 271018, China. Electronic address: j.xu@science.ru.nl. FAU - Loh, Yuin-Han AU - Loh YH AD - Cell Fate Engineering and Therapeutics Laboratory, Division of Cell Biology and Therapies, Institute of Molecular and Cell Biology, A( *)STAR, Singapore 138673, Singapore; Department of Biological Sciences, National University of Singapore, Singapore 117558, Singapore; NUS Graduate School for Integrative Sciences and Engineering Programme, National University of Singapore, Singapore 119077, Singapore; Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117593, Singapore. Electronic address: yhloh@imcb.a-star.edu.sg. LA - eng GR - R01 AG061796/AG/NIA NIH HHS/United States GR - R01 CA208517/CA/NCI NIH HHS/United States GR - RF1 AG056318/AG/NIA NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20230112 PL - United States TA - Stem Cell Reports JT - Stem cell reports JID - 101611300 RN - 0 (Tumor Suppressor Protein p53) RN - 0 (Ribosomal Proteins) RN - 0 (Chromatin) SB - IM MH - Animals MH - Mice MH - *Tumor Suppressor Protein p53/genetics/metabolism MH - *Mouse Embryonic Stem Cells/metabolism MH - Transcriptome MH - Ribosomal Proteins/genetics/metabolism MH - Chromatin/metabolism PMC - PMC9968990 OTO - NOTNLM OT - 2C-like cells OT - MERVL OT - P53 OT - RPs COIS- Conflict of interest The authors declare no competing interests. EDAT- 2023/01/14 06:00 MHDA- 2023/02/18 06:00 PMCR- 2023/01/12 CRDT- 2023/01/13 18:42 PHST- 2022/04/07 00:00 [received] PHST- 2022/12/07 00:00 [revised] PHST- 2022/12/08 00:00 [accepted] PHST- 2023/01/14 06:00 [pubmed] PHST- 2023/02/18 06:00 [medline] PHST- 2023/01/13 18:42 [entrez] PHST- 2023/01/12 00:00 [pmc-release] AID - S2213-6711(22)00596-3 [pii] AID - 10.1016/j.stemcr.2022.12.007 [doi] PST - ppublish SO - Stem Cell Reports. 2023 Feb 14;18(2):463-474. doi: 10.1016/j.stemcr.2022.12.007. Epub 2023 Jan 12.