Speaker: Yi Zhu, Ph.D., Postdoctoral Scholar, Department of Dermatology & Department of Genetics, Stanford University

Time: 13:30-14:30 p.m., Dec 26, 2024, GMT+8

Venue: Rm B101, Lui Che-woo Building, PKU

Abstract: 

O-GIcNAc is a dynamic post-translational modification (PTM) that regulates protein functions. In studying the regulatory roles of O-GINAc, a major roadblock is the inability to change O-GiNAcylation on a single protein at a time. Herein, we developed a dual RNA-aptamer-based approach that simultaneously targeted O-GINAc transferase (OGT) and S-catenin, the key transcription factor of the Wnt signaling pathway, to selectively increase O-GIcNAcylation of the latter without affecting other OGT substrates. Using the OGT/-catenin dual-specificity aptamers, we found that O-GIcNAcylation of -catenin stabilizes the protein by inhibiting its interaction with -TrCP. O-GIcNAc also increases -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-GIcNAcylation on individual proteins.

Source: School of Life Sciences, PKU