RNF219 interacts with CCR4-NOT in regulating stem cell differentiation

J Mol Cell Biol. 2020 Oct 26;12(11):894-905. doi: 10.1093/jmcb/mjaa061.

Abstract

Regulation of RNA stability plays a crucial role in gene expression control. Deadenylation is the initial rate-limiting step for the majority of RNA decay events. Here, we show that RING finger protein 219 (RNF219) interacts with the CCR4-NOT deadenylase complex. RNF219-CCR4-NOT exhibits deadenylation activity in vitro. RNA-seq analyses identify some of the 2-cell-specific genes and the neuronal genes significantly downregulated upon RNF219 knockdown, while upregulated after depletion of the CCR4-NOT subunit CNOT10 in mouse embryonic stem (ES) cells. RNF219 depletion leads to impaired neuronal lineage commitment during ES cell differentiation. Our study suggests that RNF219 is a novel interacting partner of CCR4-NOT and required for maintenance of ES cell pluripotency.

Keywords: CCR4–NOT; RNF219; deadenylation; protein complex; stem cell differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation* / genetics
  • Gene Expression Regulation
  • HEK293 Cells
  • Humans
  • Mice
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Mouse Embryonic Stem Cells / cytology*
  • Mouse Embryonic Stem Cells / metabolism*
  • Neurons / cytology
  • Neurons / metabolism
  • Polycomb Repressive Complex 1 / metabolism*
  • Protein Binding
  • Transcription Factors / metabolism*
  • Ubiquitin-Protein Ligases / metabolism*

Substances

  • Cnot10 protein, mouse
  • MicroRNAs
  • Transcription Factors
  • Polycomb Repressive Complex 1
  • Rnf2 protein, mouse
  • Ubiquitin-Protein Ligases