# CSDE1 stabilizes AGO2 in embryonic stem cells

**Authors:** Yuguan Jiang, Mason Waye, Pavan Kumar Kakumani

PMC · DOI: 10.3389/fmolb.2025.1745258 · 2026-01-15

## 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.

## Key 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.

## Linked entities

- **Genes:** CSDE1 (cold shock domain containing E1) [NCBI Gene 7812], AGO2 (argonaute RISC catalytic component 2) [NCBI Gene 27161], NANOG (Nanog homeobox) [NCBI Gene 79923], SOX2 (SRY-box transcription factor 2) [NCBI Gene 6657], POU5F1 (POU class 5 homeobox 1) [NCBI Gene 5460]
- **Proteins:** CSDE1 (cold shock domain containing E1), AGO2 (argonaute RISC catalytic component 2), NANOG (Nanog homeobox), SOX2 (SRY-box transcription factor 2), POU5F1 (POU class 5 homeobox 1)
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** Sox2 (SRY (sex determining region Y)-box 2) [NCBI Gene 20674] {aka Sox-2, lcc, ysb}, Pou5f1 (POU domain, class 5, transcription factor 1) [NCBI Gene 18999] {aka NF-A3, Oct-3, Oct-3/4, Oct-4, Oct3, Oct3/4}, Ago2 (argonaute RISC catalytic subunit 2) [NCBI Gene 239528] {aka 1110029L17Rik, 2310051F07Rik, Eif2c2, Gerp95, Gm10365, mKIAA4215}, Csde1 (cold shock domain containing E1, RNA binding) [NCBI Gene 229663] {aka D3Jfr1, mKIAA0885, unr}, Nanog (Nanog homeobox) [NCBI Gene 71950] {aka 2410002E02Rik, ENK, Stm1, ecat4}
- **Species:** Mus musculus (house mouse, species) [taxon 10090]

## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12851991/full.md

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Source: https://tomesphere.com/paper/PMC12851991