CSDE1 stabilizes AGO2 in embryonic stem cells

TL;DR

This study shows how the protein CSDE1 helps maintain stem cell properties by stabilizing AGO2 and key stem cell proteins.

Contribution

The novel finding is that CSDE1 stabilizes AGO2 and pluripotent proteins, preventing their degradation in embryonic stem cells.

Findings

CSDE1 stabilizes AGO2 and pluripotent proteins like NANOG, SOX2, and Oct4 in mouse embryonic stem cells.

CSDE1 prevents ubiquitination of AGO2 and stem cell markers.

The CSD1 domain of CSDE1 is essential for AGO2 stabilization and maintaining pluripotency.

Abstract

The cold shock domain (CSD)-containing protein, CSDE1, interacts with AGO2 and regulates miRNA function in post-transcriptional gene silencing. While the individual roles of CSDE1 and AGO2 in regulating gene expression underlying stem cell pluripotency and differentiation are well known, the effects of their interaction remain unclear. Here, we demonstrate that CSDE1 stabilizes AGO2 and key pluripotent proteins, NANOG, SOX2, and Oct4, in mouse embryonic stem cells. CSDE1 stabilizes AGO2 and the stem cell markers, preventing their ubiquitination. Further, the N-terminal domain, CSD1, which is necessary for CSDE1 interaction with AGO2, is crucial for maintaining AGO2 levels and the pluripotent proteins, thereby revealing an additional layer of control over AGO2 function and gene expression associated with stem cell fate at the post-translational level.

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