适体
生物
核糖开关
核糖核酸
细胞生物学
转录因子
抄写(语言学)
连环素
转移酶
Wnt信号通路
计算生物学
生物化学
信号转导
分子生物学
基因
非编码RNA
酶
哲学
语言学
出处
期刊:Cell
[Elsevier]
日期:2023-01-01
卷期号:186 (2): 428-445.e27
被引量:44
标识
DOI:10.1016/j.cell.2022.12.016
摘要
O-GlcNAc is a dynamic post-translational modification (PTM) that regulates protein functions. In studying the regulatory roles of O-GlcNAc, a major roadblock is the inability to change O-GlcNAcylation on a single protein at a time. Herein, we developed a dual RNA-aptamer-based approach that simultaneously targeted O-GlcNAc transferase (OGT) and β-catenin, the key transcription factor of the Wnt signaling pathway, to selectively increase O-GlcNAcylation of the latter without affecting other OGT substrates. Using the OGT/β-catenin dual-specificity aptamers, we found that O-GlcNAcylation of β-catenin stabilizes the protein by inhibiting its interaction with β-TrCP. O-GlcNAc also increases β-catenin’s interaction with EZH2, recruits EZH2 to promoters, and dramatically alters the transcriptome. Further, by coupling riboswitches or an inducible expression system to aptamers, we enabled inducible regulation of protein-specific O-GlcNAcylation. Together, our findings demonstrate the efficacy and versatility of dual-specificity aptamers for regulating O-GlcNAcylation on individual proteins.
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