生物
阿尔戈瑙特
胚胎干细胞
细胞生物学
小RNA
细胞命运测定
核糖核酸
RNA结合蛋白
RNA干扰
遗传学
基因
转录因子
作者
Qiuying Liu,Rachel M Pepin,Mariah K Novak,Katharine Maschhoff,Kailey Worner,Wenqian Hu
标识
DOI:10.1016/j.devcel.2024.02.006
摘要
Argonaute (AGO) proteins are evolutionarily conserved RNA-binding proteins that control gene expression through the small RNAs they interact with. Whether AGOs have regulatory roles independent of RNAs, however, is unknown. Here, we show that AGO1 controls cell fate decisions through facilitating protein folding. We found that in mouse embryonic stem cells (mESCs), while AGO2 facilitates differentiation via the microRNA (miRNA) pathway, AGO1 controls stemness independently of its binding to small RNAs. We determined that AGO1 specifically interacts with HOP, a co-chaperone for the HSP70 and HSP90 chaperones, and enhances the folding of a set of HOP client proteins with intrinsically disordered regions. This AGO1-mediated facilitation of protein folding is important for maintaining stemness in mESCs. Our results demonstrate divergent functions between AGO1 and AGO2 in controlling cellular states and identify an RNA-independent function of AGO1 in controlling gene expression and cell fate decisions.
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