Taxonomic distribution of proteins containing CPSF73-100_C domains

The tree below includes only several representative species and genera. The complete taxonomic breakdown of all proteins containing CPSF73-100_C domains can be accessed here. Click the counts or percentage values to display the corresponding proteins.

Polyadenylation factor CPSF-73 is the pre-mRNA 3'-end-processingendonuclease.

Mandel CR, Kaneko S, Zhang H, Gebauer D, Vethantham V, Manley JL, Tong L
Nature. 2006; 444: 953-6

Most eukaryotic messenger RNA precursors (pre-mRNAs) undergo extensivematurational processing, including cleavage and polyadenylation at the3'-end. Despite the characterization of many proteins that are requiredfor the cleavage reaction, the identity of the endonuclease is not known.Recent analyses indicated that the 73-kDa subunit of cleavage andpolyadenylation specificity factor (CPSF-73) might be the endonuclease forthis and related reactions, although no direct data confirmed this. Herewe report the crystal structures of human CPSF-73 at 2.1 A resolution,complexed with zinc ions and a sulphate that might mimic the phosphategroup of the substrate, and the related yeast protein CPSF-100 (Ydh1) at2.5 A resolution. Both CPSF-73 and CPSF-100 contain two domains, ametallo-beta-lactamase domain and a novel beta-CASP (named formetallo-beta-lactamase, CPSF, Artemis, Snm1, Pso2) domain. The active siteof CPSF-73, with two zinc ions, is located at the interface of the twodomains. Purified recombinant CPSF-73 possesses RNA endonuclease activity,and mutations that disrupt zinc binding in the active site abolish thisactivity. Our studies provide the first direct experimental evidence thatCPSF-73 is the pre-mRNA 3'-end-processing endonuclease.