We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Polyadenylation factor CPSF-73 is the pre-mRNA 3'-end-processing endonuclease.
- Authors
Mandel, Corey R; Kaneko, Syuzo; Zhang, Hailong; Gebauer, Damara; Vethantham, Vasupradha; Manley, James L; Tong, Liang
- Abstract
Most eukaryotic messenger RNA precursors (pre-mRNAs) undergo extensive maturational processing, including cleavage and polyadenylation at the 3'-end. Despite the characterization of many proteins that are required for the cleavage reaction, the identity of the endonuclease is not known. Recent analyses indicated that the 73-kDa subunit of cleavage and polyadenylation specificity factor (CPSF-73) might be the endonuclease for this and related reactions, although no direct data confirmed this. Here we report the crystal structures of human CPSF-73 at 2.1 A resolution, complexed with zinc ions and a sulphate that might mimic the phosphate group of the substrate, and the related yeast protein CPSF-100 (Ydh1) at 2.5 A resolution. Both CPSF-73 and CPSF-100 contain two domains, a metallo-beta-lactamase domain and a novel beta-CASP (named for metallo-beta-lactamase, CPSF, Artemis, Snm1, Pso2) domain. The active site of CPSF-73, with two zinc ions, is located at the interface of the two domains. Purified recombinant CPSF-73 possesses RNA endonuclease activity, and mutations that disrupt zinc binding in the active site abolish this activity. Our studies provide the first direct experimental evidence that CPSF-73 is the pre-mRNA 3'-end-processing endonuclease.
- Publication
Nature, 2006, Vol 444, Issue 7121, p953
- ISSN
1476-4687
- Publication type
Journal Article
- DOI
10.1038/nature05363