RBFOX2 recognizes N⁶-methyladenosine to suppress transcription and block myeloid leukaemia differentiation.

ABSTRACT: N⁶-methyladenosine (m⁶A) methylation can be deposited on chromatin-associated RNAs (caRNAs) by the RNA methyltransferase complex (MTC) to regulate chromatin state and transcription. However, the mechanism by which MTC is recruited to distinct genomic loci remains elusive. Here we identify RBFOX2, a well-studied RNA-binding protein, as a chromatin factor that preferentially recognizes m⁶A on caRNAs. RBFOX2 can recruit RBM15, an MTC component, to facilitate methylation of promoter-associated RNAs. RBM15 also physically interacts with YTHDC1 and recruits polycomb repressive complex 2 (PRC2) to the RBFOX2-bound loci for chromatin silencing and transcription suppression. Furthermore, we found that this RBFOX2/m⁶A/RBM15/YTHDC1/PRC2 axis plays a critica

SUBMITTER: Dou X 

PROVIDER: S-EPMC10495261 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature