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

Yao Yi, Yingying Zeng, Tsz Wing Sam, Kiyofumi Hamashima, Rachel Jun Rou Tan, Tushar Warrier, Jun Xiang Phua, Reshma Taneja, Yih Cherng Liou, Hu Li, Jian Xu, Yuin Han Loh

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)463-474
Number of pages12
JournalStem Cell Reports
Volume18
Issue number2
DOIs
StatePublished - Feb 14 2023

Keywords

  • 2C-like cells
  • MERVL
  • P53
  • RPs

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Developmental Biology
  • Cell Biology

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