2. Academic Validation
  3. ZFP207 sustains pluripotency by coordinating OCT4 stability, alternative splicing and RNA export

ZFP207 sustains pluripotency by coordinating OCT4 stability, alternative splicing and RNA export

  • EMBO Rep. 2022 Feb 3;23(3):e53191. doi: 10.15252/embr.202153191.
Sandhya Malla  # 1 2 3,  Devi Prasad Bhattarai  # 1 2 3,  Paula Groza 2 3,  Dario Melguizo-Sanchis 1 3,  Ionut Atanasoai 4,  Carlos Martinez-Gamero 2 3,  Ángel-Carlos Román 5,  Dandan Zhu 6,  Dung-Fang Lee 6 7 8 9,  Claudia Kutter 4,  Francesca Aguilo 1 2 3
Affiliations

Affiliations

  • 1 Department of Medical Biosciences, Umeå University, Umeå, Sweden.
  • 2 Department of Molecular Biology, Umeå University, Umeå, Sweden.
  • 3 Wallenberg Centre for Molecular Medicine, Umeå University, Umeå, Sweden.
  • 4 Department of Microbiology, Tumor and Cell Biology, Science for Life Laboratory, Karolinska Institute, Stockholm, Sweden.
  • 5 Department of Biochemistry, Molecular Biology and Genetics, University of Extremadura, Badajoz, Spain.
  • 6 Department of Integrative Biology and Pharmacology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA.
  • 7 Center for Precision Health, School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX, USA.
  • 8 The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, TX, USA.
  • 9 Center for Stem Cell and Regenerative Medicine, The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, The University of Texas Health Science Center at Houston, Houston, TX, USA.
  • # Contributed equally.
PMID: 35037361 DOI: 10.15252/embr.202153191
Abstract

The pluripotent state is not solely governed by the action of the core transcription factors OCT4, SOX2, and NANOG, but also by a series of co-transcriptional and post-transcriptional events, including alternative splicing (AS) and the interaction of RNA-binding proteins (RBPs) with defined subpopulations of RNAs. Zinc Finger Protein 207 (ZFP207) is an essential transcription factor for mammalian embryonic development. Here, we employ multiple functional analyses to characterize its role in mouse embryonic stem cells (ESCs). We find that ZFP207 plays a pivotal role in ESC maintenance, and silencing of Zfp207 leads to severe neuroectodermal differentiation defects. In striking contrast to human ESCs, mouse ZFP207 does not transcriptionally regulate neuronal and stem cell-related genes but exerts its effects by controlling AS networks and by acting as an RBP. Our study expands the role of ZFP207 in maintaining ESC identity, and underscores the functional versatility of ZFP207 in regulating neural fate commitment.

Keywords

RNA-binding protein; ZFP207; Zinc finger protein; alternative splicing; pluripotency.

Figures
Products