Small-Molecule Ebselen Binds to YTHDF Proteins Interfering with the Recognition of N ⁶-Methyladenosine-Modified RNAs.

ABSTRACT: YTHDF proteins bind the N ⁶-methyladenosine (m6A)-modified mRNAs, influencing their processing, stability, and translation. Therefore, the members of this protein family play crucial roles in gene regulation and several physiological and pathophysiological conditions. YTHDF proteins contain a hydrophobic pocket that accommodates the m6A embedded in the RRACH consensus sequence on mRNAs. We exploited the presence of this cage to set up an m6A-competitive assay and performed a high-throughput screen aimed at identifying ligands binding in the m6A pocket. We report the organoselenium compound ebselen as the first-in-class inhibitor of the YTHDF m6A-binding domain. Ebselen, whose interaction with YTHDF proteins was validated via orthogonal assays, cannot discriminate b

SUBMITTER: Micaelli M 

PROVIDER: S-EPMC9578143 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature