Fig. 3

Core pre-mRNA 3’end processing factors. a The CPSF complex can recognize the AAUAAA hexamer and directly bind to the poly(A) site through CPSF4 and WDR33. CPSF3 is an endonuclease which preferentially targets cleavage sites containing CA elements. FIP1 binds to U-rich elements located upstream of the hexamer through its C-terminal domain, thereby modulating PAS recognition. It can also interact with PAP that is involved in cleavage. The CSTF complex is composed of dimers which can recognize and interact with U- and GU- rich elements downstream. CSTF can also interact with RBBP6, another important APA regulator. The CFI complex which contains CFIm68/59 and CFIm25, binds to the UGUA sequence as dimers in a similar manner to CSTF. As a part of the CFII complex it is responsible for the cleavage process. Both PAP and CFII are weakly or transiently involved in the pre-mRNA 3’end processing. Symplekin and RNA Pol II carboxy-terminal domain (CTD) have an impact on this interaction as scaffolds. b WDR33 recognizes the poly(A) signal and interacts with the AAUAAA hexamer directly. CPSF4 binds to the AAUAAA hexamer via its two zinc finger domains ZF2 and ZF3. c CLP1 and PCF11 interact via key residues of PCF11 which are highly conserved across eukaryotes. The mRNA binding is mediated by the two zinc finger domains of PCF11. The PCF11-CLP1 complex (CFII) targets the cleavage site which is located preferentially after a cytosine. d CPSF2, CPSF3 and symplekin can form a functional complex and interact with different accessory proteins to complete the maturation of pre-mRNAs