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

Sandhya Malla, Devi Prasad Bhattarai, Paula Groza, Dario Melguizo-Sanchis, Ionut Atanasoai, Carlos Martinez-Gamero, Ángel-Carlos Román, Dandan Zhu, Dung-Fang Lee, Claudia Kutter, Francesca Aguilo

EMBO reports 2022 Feb 03

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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. © 2022 The Authors. Published under the terms of the CC BY 4.0 license.

Citation

Sandhya Malla, Devi Prasad Bhattarai, Paula Groza, Dario Melguizo-Sanchis, Ionut Atanasoai, Carlos Martinez-Gamero, Ángel-Carlos Román, Dandan Zhu, Dung-Fang Lee, Claudia Kutter, Francesca Aguilo. ZFP207 sustains pluripotency by coordinating OCT4 stability, alternative splicing and RNA export. EMBO reports. 2022 Feb 03;23(3):e53191