@article{f3a254e62d63485eb637d0b4e12fa597,
title = "A conformational switch in PRP8 mediates metal ion coordination that promotes pre-mRNA exon ligation",
abstract = "Splicing of pre-mRNAs in eukaryotes is catalyzed by the spliceosome, a large RNA-protein metalloenzyme. The catalytic center of the spliceosome involves a structure comprising the U2 and U6 snRNAs and includes a metal bound by U6 snRNA. The precise architecture of the splicesome active site, however, and the question of whether it includes protein components, remains unresolved. A wealth of evidence places the protein PRP8 at the heart of the spliceosome through assembly and catalysis. Here we provide evidence that the RNase H domain of PRP8 undergoes a conformational switch between the two steps of splicing, rationalizing yeast prp8 alleles that promote either the first or second step. We also show that this switch unmasks a metal-binding site involved in the second step. Together, these data establish that PRP8 is a metalloprotein that promotes exon ligation within the spliceosome.",
author = "Schellenberg, {Matthew J.} and Tao Wu and Ritchie, {Dustin B.} and Sebastian Fica and Staley, {Jonathan P.} and Atta, {Karim A.} and Paul Lapointe and Macmillan, {Andrew M.}",
note = "Funding Information: This work was supported by an Operating grant to A.M.M. from the Canadian Institutes of Health Research (CIHR) and a US National Institutes of Health grant to J.P.S. and J. Piccirilli (R01GM088656). We would like to thank M. Friis and M. Schultz for helpful advice, J. Beggs (University of Edinburgh, Edinburgh, UK) and C. Guthrie (University of California, San Francisco, San Francisco, California, USA) for providing yeast strains and plasmids and D. Brow (University of Wisconsin–Madison, Madison, Wisconsin, USA) for providing the PRP8 V1862Y plasmid. Research described in this paper was performed at the Advanced Light Source (Berkeley, California, USA; supported by the US Department of Energy under contract no. DE-AC02-05CH11231) and the Canadian Light Source (supported by the Natural Sciences and Engineering Research Council of Canada, the National Research Council Canada, CIHR, the Province of Saskatchewan, Western Economic Diversification Canada and the University of Saskatchewan).",
year = "2013",
month = jun,
doi = "10.1038/nsmb.2556",
language = "English (US)",
volume = "20",
pages = "728--734",
journal = "Nature Structural and Molecular Biology",
issn = "1545-9993",
publisher = "Nature Publishing Group",
number = "6",
}