Figure 8. Model of APA regulation by YTHDC1.

1. YTHDC1 is associated with Pol II during transcription by interacting with MTC and binds to the modification sites upstream of proximal APA sites when m⁶A modification is finished. Then, YTHDC1 interacts with FIP1L1 and disrupts the recruitment of CPSF4 and other CPSF factors, resulting in the suppression of proximal APA sites and longer 3′ UTRs.
2. This inhibition is abrogated at low levels of YTHDC1 or in the absence of m⁶A modification. FIP1L1 interacts with CPSF4, which recruits other CPSF factors and promotes the usage of proximal APA sites, resulting in shortened 3′ UTRs.