Year: 2008
Type: article
Abstract: Cleavage factor I(m) is an essential component of the pre-messenger RNA 3'-end processing machinery in higher eukaryotes, participating in both the polyadenylation and cleavage steps. Cleavage factor I(m) is an oligomer composed of a small 25 kDa subunit (CF I(m)25) and a variable larger subunit of either 59, 68 or 72 kDa. The small subunit also interacts with RNA, poly(A) polymerase, and the nuclear poly(A)-binding protein. These protein-protein interactions are thought to be facilitated by the Nudix domain of CF I(m)25, a hydrolase motif with a characteristic alpha/beta/alpha fold and a conserved catalytic sequence or Nudix box. We present here the crystal structures of human CF I(m)25 in its free and diadenosine tetraphosphate (Ap(4)A) bound forms at 1.85 and 1.80 A, respectively. CF I(m)25 crystallizes as a dimer and presents the classical Nudix fold. Results from crystallographic and biochemical experiments suggest that CF I(m)25 makes use of its Nudix fold to bind but not hydrolyze ATP and Ap(4)A. The complex and apo protein structures provide insight into the active oligomeric state of CF I(m) and suggest a possible role of nucleotide binding in either the polyadenylation and/or cleavage steps of pre-messenger RNA 3'-end processing.
Source: Nucleic Acids Research
DOI: 10.1093/nar/gkn079
Authors: Molly Coseno, Georges Martin, Christopher Berger, Gregory Gilmartin, Walter Keller, Sylvie Doublié
Institutions: University of Vermont, University of Basel
Language: English
Topic: RNA Research and Splicing
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,992
Funders: National Science Foundation, U.S. Department of Energy, Universität Basel, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, National Institutes of Health, Office of Science, National Cancer Institute, National Institute of General Medical Sciences, Argonne National Laboratory, Brookhaven National Laboratory
Awards: G1126863173, G1313983767, G132563423, G1336448005, G1468070684, CRYSTALLOGRAPHIC STUDIES OF EUKARYOTIC POLY(A)POLYMERASE, G1572106353, G2219523378, G222407312, G2363639003, G2731844474, G3351052168, G338944111, G3897559065, G402281873, G4385809619, G4866076653, G498139845, G5019921669, G5094664921, G516474873, G5292656900, G6004781752, G719843099, G7688398576, G969889393
OpenAlex ID: W2139253560