Fig. 2

The APA complex and its machinery. CFIm complex binds to the conserved upstream UGUA region to mediate the cleavage reaction and recruit other proteins, including CPSF and CSTF. After combining with PAP, this complex translocates through the pre-mRNA in a 5′ to 3′ fashion. Upon arrival at the AAUAAA region, the adenosine acidification signal CPSF recognizes the polyadenylation signal AAUAAA and CPSF73 cleaves the mRNA. CSTF then binds to the GU- or U-rich sequence. The U-rich region bound to the FIP1L1 subunit of the CPSF is located between the polyadenylation signal AAUAAA and the cleavage site. Symplekin functions as a scaffold protein and PAPs catalyze the addition of untemplated adenosines. Generally, the usage of the proximal pAs generates short isoforms and the translation can be suppressed, often resulting in less protein