Targeting O-GlcNAcylated METTL3 impedes MDS/AML progression via diminishing SRSF1 m⁶A modification.

ABSTRACT: N6-methyladenosine (m⁶A) modification, primarily regulated by methyltransferase-like protein 3 (METTL3), plays a pivotal role in RNA metabolism and leukemogenesis. However, the post-translational mechanisms governing METTL3 stability and function remain incompletely understood. Given the widespread occurrence of O-GlcNAcylation on nuclear and cytosolic proteins, we hypothesized that METTL3 might undergo O-GlcNAcylation, thereby influencing its stability and oncogenic function in myeloid malignancies. In this study, we found that METTL3 is O-GlcNAcylated in both myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), and its expression positively correlates with O-GlcNAcylation levels. Functional assays demonstrated that O-GlcNAcylation enhances METTL3 protein stability

SUBMITTER: Gou J 

PROVIDER: S-EPMC12703143 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature