Ribosomal proteins regulate 2-cell-stage transcriptome in mouse embryonic stem cells

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 exp...

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Main Authors: Yi, Yao, Zeng, Yingying, Sam, Tsz Wing, Hamashima, Kiyofumi, Tan, Rachel Jun Rou, Warrier, Tushar, Phua, Jun Xiang, Taneja, Reshma, Liou, Yih-Cherng, Li, Hu, Xu, Jian, Loh, Yuin-Han
Other Authors: School of Biological Sciences
Format: Article
Language:English
Published: 2023
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Online Access:https://hdl.handle.net/10356/169689
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Institution: Nanyang Technological University
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spelling sg-ntu-dr.10356-1696892023-07-31T15:32:19Z Ribosomal proteins regulate 2-cell-stage transcriptome in mouse embryonic stem cells Yi, Yao Zeng, Yingying Sam, Tsz Wing Hamashima, Kiyofumi Tan, Rachel Jun Rou Warrier, Tushar Phua, Jun Xiang Taneja, Reshma Liou, Yih-Cherng Li, Hu Xu, Jian Loh, Yuin-Han School of Biological Sciences Institute of Molecular and Cell Biology, A*STAR Science::Biological sciences 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. Agency for Science, Technology and Research (A*STAR) National Research Foundation (NRF) Published version H.L. is supported by National Institutes of Health (AG056318, AG61796, and CA208517); the Glenn Foundation for Medical Research; Mayo Clinic Center for Biomedical Discovery; Center for Individualized Medicine, Mayo Clinic; Mayo Clinic Cancer Center; and the David F. and Margaret T. Grohne Cancer Immunology and Immunotherapy Program. J.X. is supported by the Institute for Water and Wetland Research, Radboud University; by the Department of Biological Sciences, National University of Singapore; and by the Joint Center for Single Cell Biology, Radboud University-Shanghai Jiao Tong University-Shandong Agricultural University. Y.-H.L. is supported by the NRF Investigatorship award - NRFI2018-02; IAF-PP grant - H1801a0021; NRF grant - NRF2019-THE002-0001; NMRC grant - OFIRG21nov-0088; A*STAR grants - W22W3D0007 and C211318012; and A*STAR BMRC - Use-Inspired Basic Research award. We are grateful to the Biomedical Research Council, Agency for Science, Technology and Research, Singapore, for research funding. 2023-07-31T05:19:16Z 2023-07-31T05:19:16Z 2023 Journal Article Yi, Y., Zeng, Y., Sam, T. W., Hamashima, K., Tan, R. J. R., Warrier, T., Phua, J. X., Taneja, R., Liou, Y., Li, H., Xu, J. & Loh, Y. (2023). Ribosomal proteins regulate 2-cell-stage transcriptome in mouse embryonic stem cells. Stem Cell Reports, 18(2), 463-474. https://dx.doi.org/10.1016/j.stemcr.2022.12.007 2213-6711 https://hdl.handle.net/10356/169689 10.1016/j.stemcr.2022.12.007 36638791 2-s2.0-85147680892 2 18 463 474 en NRFI2018-02 H1801a0021 NRF-THE002-0001 OFIRG21nov-0088 W22W3D0007 C211318012 Stem Cell Reports © 2022 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Science::Biological sciences
spellingShingle Science::Biological sciences
Yi, Yao
Zeng, Yingying
Sam, Tsz Wing
Hamashima, Kiyofumi
Tan, Rachel Jun Rou
Warrier, Tushar
Phua, Jun Xiang
Taneja, Reshma
Liou, Yih-Cherng
Li, Hu
Xu, Jian
Loh, Yuin-Han
Ribosomal proteins regulate 2-cell-stage transcriptome in mouse embryonic stem cells
description 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.
author2 School of Biological Sciences
author_facet School of Biological Sciences
Yi, Yao
Zeng, Yingying
Sam, Tsz Wing
Hamashima, Kiyofumi
Tan, Rachel Jun Rou
Warrier, Tushar
Phua, Jun Xiang
Taneja, Reshma
Liou, Yih-Cherng
Li, Hu
Xu, Jian
Loh, Yuin-Han
format Article
author Yi, Yao
Zeng, Yingying
Sam, Tsz Wing
Hamashima, Kiyofumi
Tan, Rachel Jun Rou
Warrier, Tushar
Phua, Jun Xiang
Taneja, Reshma
Liou, Yih-Cherng
Li, Hu
Xu, Jian
Loh, Yuin-Han
author_sort Yi, Yao
title Ribosomal proteins regulate 2-cell-stage transcriptome in mouse embryonic stem cells
title_short Ribosomal proteins regulate 2-cell-stage transcriptome in mouse embryonic stem cells
title_full Ribosomal proteins regulate 2-cell-stage transcriptome in mouse embryonic stem cells
title_fullStr Ribosomal proteins regulate 2-cell-stage transcriptome in mouse embryonic stem cells
title_full_unstemmed Ribosomal proteins regulate 2-cell-stage transcriptome in mouse embryonic stem cells
title_sort ribosomal proteins regulate 2-cell-stage transcriptome in mouse embryonic stem cells
publishDate 2023
url https://hdl.handle.net/10356/169689
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