O-GlcNAcylation promotes the cytosolic localization of the m⁶A reader YTHDF1 and colorectal cancer tumorigenesis.

ABSTRACT: O-linked GlcNAc (O-GlcNAc) is an emerging post-translation modification that couples metabolism with cellular signal transduction by crosstalk with phosphorylation and ubiquitination to orchestrate various biological processes. The mechanisms underlying the involvement of O-GlcNAc modifications in N⁶-methyladenosine (m⁶A) regulation are not fully characterized. Herein, we show that O-GlcNAc modifies the m⁶A mRNA reader YTH domain family 1 (YTHDF1) and fine-tunes its nuclear translocation by the exportin protein Crm1. First, we present evidence that YTHDF1 interacts with the sole O-GlcNAc transferase (OGT). Second, we verified Ser196/Ser197/Ser198 as the YTHDF1 O-GlcNAcylation sites, as described in numerous chemoproteomic studies. Then we constructed the O-

SUBMITTER: Li J 

PROVIDER: S-EPMC10208891 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature