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

ABSTRACT: 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.

SUBMITTER: Yi Y

PROVIDER: S-EPMC9968990 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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

Yi Yao Y Zeng Yingying Y Sam Tsz Wing TW Hamashima Kiyofumi K Tan Rachel Jun Rou RJR Warrier Tushar T Phua Jun Xiang JX Taneja Reshma R Liou Yih-Cherng YC Li Hu H Xu Jian J Loh Yuin-Han YH

Stem cell reports 20230112 2

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 R ...[more]

PMID: 36638791

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