The STAT3 Target Mettl8 Regulates Mouse ESC Differentiation via Inhibiting the JNK Pathway

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. In this article, Fu and colleagues show that STAT3 positively regulates gene expression of Mettl8 in mouse ESCs. METTL8 is dispensable for pluripotency but affects ESC differentiation by interacting with Mapkbp1 mRNA and inhibiting its translation. MAPKBP1 mediates the effect of METTL8 to JNK signaling during mouse ESC differentiation. © 2018 The Author(s)