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

Stem Cell Reports

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:

Published: February 2023

AI Article Synopsis

  • A rare population of mouse embryonic stem cells (mESCs), known as 2-cell-like cells, is characterized by specific gene expressions related to early embryonic stages.
  • This study highlights the importance of certain ribosomal proteins (RPs) in maintaining the identity of these mESCs and regulating the expression of early-stage specific genes.
  • Disruption of these RPs leads to changes in gene expression and chromatin structure, primarily involving the activation of pathways linked to the P53 protein and its downstream effects on 2C transcript expression.

Article 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9968990PMC
http://dx.doi.org/10.1016/j.stemcr.2022.12.007DOI Listing

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