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The STAT3 Target Mettl8 Regulates Mouse ESC Differentiation via Inhibiting the JNK Pathway. (Stem Cell Reports, Apr 2018)

Gu H1, Do DV2, Liu X3, Xu L3, Su Y4, Nah JM5, Wong Y3, Li Y3, Sheng N6, Tilaye GA4, Yang H3, Guo H5, Yan J6, Fu XY7.

Author Information
1Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore, 117599; Centre for Life Sciences, National University of Singapore, Singapore, Singapore, 117456.
2Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore, 117456; Genome Institute of Singapore, Singapore, Singapore, 138672.
3Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore, 117599.
4Centre for Life Sciences, National University of Singapore, Singapore, Singapore, 117456; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore, 117456.
5Institute of Molecular and Cell Biology, Singapore, Singapore, 138673.
6Model Animal Research Center, Nanjing University, Nanjing, China, 210061.
7Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore, 117599; Centre for Life Sciences, National University of Singapore, Singapore, Singapore, 117456; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore, 117456; Department of Biology, Southern University of Science and Technology, Shenzhen, China, 518055.

Abstract

The capacity of embryonic stem cells (ESCs) to differentiate into all lineages of mature organism is precisely regulated by cellular signaling factors. STAT3 is a crucial transcription factor that plays a central role in maintaining ESC identity. However, the underlying mechanism by which STAT3 directs differentiation is still not completely understood. Here, we show that STAT3 positively regulates gene expression of methyltransferase-like protein 8 (Mettl8) in mouse ESCs. We found that METTL8 is dispensable for pluripotency but affects ESC differentiation. Subsequently, we discovered that METTL8 interacts with Mapkbp1’s mRNA, which is an intermediate factor in c-Jun N-terminal kinase (JNK) signaling, and inhibits the translation of the mRNA. Thereby, METTL8 prohibits the activation of JNK signaling and enhances the differentiation of mouse ESCs. Collectively, our study uncovers a STAT3 target, Mettl8, which regulates mouse ESC differentiation via JNK signaling.

KEYWORDS:

JNKMettl8STAT3differentiation; embryonic stem cell

PMID:  29706498