Rbm46 regulates mouse embryonic stem cell differentiation by targeting β-Catenin mRNA for degradation

PLoS One. 2017 Feb 17;12(2):e0172420. doi: 10.1371/journal.pone.0172420. eCollection 2017.

Abstract

Embryonic stem cells (ESCs) are pluripotent cells and have the capability for differentiation into any of the three embryonic germ layers. The Wnt/β-Catenin pathway has been shown to play an essential role in ESC differentiation regulation. Activation of β-Catenin by post-translational modification has been extensively studied. However, mechanism(s) of post-transcriptional regulation of β-Catenin are not well defined. In this study, we report an RNA recognition motif-containing protein (RNA binding motif protein 46, RBM46) which regulates the degradation of β-Catenin mRNA. Our results show that Rbm46 is distributed primarily in the cytoplasm of mouse ESCs (mESCs) and is elevated during the process of ESC differentiation. In addition, overexpression of Rbm46 results in differentiation of mESCs into trophectoderm, while knock-down of Rbm46 leads to mESC differentiation into endoderm. β-Catenin, a key effector in the Wnt pathway which has been reported to play a significant role in the regulation of ESC differentiation, is post-transcriptionally regulated by Rbm46. Our study reveals Rbm46 plays a novel role in the regulation of ESC differentiation.

Publication types

  • Retracted Publication

MeSH terms

  • Animals
  • Cell Differentiation / genetics*
  • Cells, Cultured
  • Endoderm / cytology
  • Endoderm / physiology
  • Gene Expression Regulation
  • Gene Knockdown Techniques
  • Mice
  • Mouse Embryonic Stem Cells / cytology*
  • Mouse Embryonic Stem Cells / physiology
  • RNA Stability
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • beta Catenin / genetics*
  • beta Catenin / metabolism

Substances

  • CTNNB1 protein, mouse
  • Rbm46 protein, mouse
  • RNA-Binding Proteins
  • beta Catenin

Grants and funding

This work was supported by the International S&T Cooperation Program (grant no. 2011DFA31040) and the 863 Program (grant no. 2011AA020106) from the Ministry of Science and Technology of China, the New Drug Innovation of China (grant no. 2011ZX09102-010-02), a grant from Strategic Priority Research Program of the Chinese Academy of Sciences (grant no. XDA01040000), and a special grant from Shanghai Bureau of Science and Technology (grant no. 12DZ1910900). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.