Bachelor of Science, Tsinghua University (2009)
Doctor of Philosophy, Johns Hopkins University (2019)
B.S., Tsinghua University, Biological Sciences (2009)
Ph.D., Johns Hopkins University, Biochemistry (2019)
Howard Chang, Postdoctoral Faculty Sponsor
Dual-specificity RNA aptamers enable manipulation of target-specific O-GlcNAcylation and unveil functions of O-GlcNAc on beta-catenin.
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 beta-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/beta-catenin dual-specificity aptamers, we found that O-GlcNAcylation of beta-catenin stabilizes the protein by inhibiting its interaction with beta-TrCP. O-GlcNAc also increases beta-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.
View details for DOI 10.1016/j.cell.2022.12.016
View details for PubMedID 36626902