Figure 7.

Cooperative role of m⁶A in regulating SRSF2 function at splice sites. The splicing factor SRSF2 can recognize exon splicing enhancer (ESE), inducing exon inclusion. METTL3-mediated m⁶A modification enhances the recruitment of SRSF2 to its target ESE, promoting exon inclusion. On the other hand demethylation of m⁶A-RRACHs near ESEs by FTO prevents recognition of the ESEs by SRSF2, thereby inhibiting inclusion and instead promoting exon skipping of the specific exon. M⁶A co-regulated by methyltransferases and demthylases serves as a new RNA splicing exonic cis-regulatory element that in combination with ESEs regulates SRSF2 protein recruitment.