Fig. 8

Model of pPAS usage regulated by SRSF7, SRSF3, and CFIm. a Model of regulation of pPAS usage and 3′UTR-APA by SRSF7 and SRSF3. Left panel: High SRSF7 levels and binding upstream of pPASs enhance pPAS usage through the recruitment of FIP1—transcripts with short 3′UTRs. Middle panel: High SRSF3 levels and binding upstream of pPASs prevent SRSF7 binding and pPAS enhancement. High levels and binding of CFIm upstream of dPASs enhances dPAS usage instead—transcripts with long 3′UTRs. Right panel: Srsf3 KD results in reduced CFIm levels. The dPAS is no longer enhanced by CFIm binding, instead SRSF7 binding at pPASs enhances their usage – transcripts with short 3′UTRs. b Model of pPAS inhibition by CFIm. Top: CFIm binding immediately up- and downstream of the pPAS inhibits its usage by looping out the CSEs or DSEs, leading to unproductive FIP1 recruitment – no cleavage – transcripts with long 3′UTRs. 5—CPSF5. Bottom: Depletion of SRSF3 or CPSF6 leads to low CFIm levels, which unmasks pPASs and allows their activation—transcripts with short 3′UTRs.