Cleavage And Polyadenylation Specific Factor 3 (CPSF3)

A poly(A) tail is added to eukaryotic mRNA precursors after tightly coupled cleavage and polyadenylation reactions at their 3-prime ends. The factor responsible for this activity, CPSF, contains multiple subunits (e.g., CPSF1).the crystal structures of human CPSF73 at 2.1-angstrom resolution, complexed with zinc ions and a sulfate that might mimic the phosphate group of substrate, and the related yeast protein CPSF100 (CPSF2) at 2.5-angstrom resolution. Both CPSF73 and CPSF100 contain 2 domains, a metallo-beta-lactamase domain and a novel beta-CASP domain. The active site of CPSF73, with 2 zinc ions, is located at the interface of the 2 domains. Purified recombinant CPSF73 possesses RNA endonuclease activity, and mutations that disrupt zinc binding in the active site abolish this activity.