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SOX2 interacts with hnRNPK to modulate alternative splicing in mouse embryonic stem cells
Yanlan Huang1, Yuxuan Liu1, Mingyi Pu1
1School of Medicine, Shenzhen Campus of Sun Yat-Sen University, Shenzhen, 518107, People's Republic of China.
Cell & Bioscience
|August 19, 2024
Summary
SOX2 and heterogeneous nuclear ribonucleoprotein K (hnRNPK) are crucial for maintaining pluripotency in mouse embryonic stem cells. hnRNPK interacts with SOX2 to regulate alternative splicing of key pluripotency genes.
Area of Science:
- * Molecular and Cellular Biology
- * Developmental Biology
- * Gene Regulation
Background:
- * SOX2 is a key transcription factor controlling stemness and differentiation.
- * SOX2's function is modulated by its interaction partners, including heterogeneous nuclear ribonucleoproteins (hnRNPs).
- * The specific roles of hnRNPs in SOX2-mediated gene expression remain largely uncharacterized.
Purpose of the Study:
- * To investigate the functional relationship between SOX2 and hnRNPK in maintaining pluripotency.
- * To elucidate the molecular mechanisms underlying SOX2-hnRNPK collaboration in gene expression regulation.
Main Methods:
- * Protein-protein interaction studies.
- * RNA sequencing (RNA-seq) analysis.
- * Analysis of SOX2-DNA and SOX2-pre-mRNA interactions.
Main Results:
- * Co-existence of SOX2 and hnRNPK is essential for mouse embryonic stem cell (mESC) pluripotency.
- * hnRNPK directly interacts with the SOX2 DNA-binding domain and affects the 7SK snRNP complex.
- * hnRNPK enhances SOX2 interaction with pre-mRNAs and regulates alternative splicing of pluripotency genes, without impacting SOX2-mediated transcription initiation or elongation.
Conclusions:
- * SOX2 and hnRNPK engage in a direct protein-protein interaction.
- * hnRNPK collaborates with SOX2 to regulate alternative splicing in mESCs, contributing to pluripotency maintenance.
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