Abstract
The human p100 protein is a vital transcription regulator that increases gene transcription by forming a physical bridge between promoter-specific activators and the basal transcription machinery. Here we demonstrate that the tudor and SN (TSN) domain of p100 interacts with U small nuclear ribonucleoprotein (snRNP) complexes, suggesting a role for p100 in the processing of precursor messenger RNA. We determined the crystal structure of the p100 TSN domain to delineate the molecular basis of p100's proposed functions. The interdigitated structure resembles a hook, with a hinge controlling the movement and orientation of the hook. Our studies suggest that a conserved aromatic cage hooks methyl groups of snRNPs and anchors p100 to the spliceosome. These structural insights partly explain the distinct roles of p100 in transcription and splicing.
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Acknowledgements
This work was funded by the 863 (grant 2006AA02A316) and 973 (grant 2006CB910901) projects of the Ministry of Science and Technology of China, the National Natural Science Foundation of China (grants 30670427, 30670441 and 30300070), the US National Institutes of Health (grant 1P50 GM62407), the University of Georgia Research Foundation, the Georgia Research Alliance, Program for New Century Excellent Talents in University (grant NCET-04-0245), Tianjin Municipal Science and Technology Commission (grant 07JCZDJC07300) and the Institute of Biophysics, Chinese Academy of Sciences. Supporting institutions for the SER-CAT 22-ID beamline at the Advanced Photon Source may be found at http://www.ser-cat.org/members.html. Use of the Advanced Photon Source was supported by the US Department of Energy, Office of Science, Office of Basic Energy Sciences, under contract number W-31-109-Eng-38.
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N.S., M.Z., C.C. and H.X. contributed to the structural studies. J.Y., J.S., Y.D. and O.S. contributed to the mutagenesis and functional characterization of the p100 TSN domain. Z.J.-L., Y.L. and Z.Y. contributed to data collection and analysis. Z.-J.L., J.Y., Z. R. and B.-C.W. conceived the study and participated in its design and coordination. N.S., Z.-J.L., O.S. and J.Y. drafted the manuscript.
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Shaw, N., Zhao, M., Cheng, C. et al. The multifunctional human p100 protein 'hooks' methylated ligands. Nat Struct Mol Biol 14, 779–784 (2007). https://doi.org/10.1038/nsmb1269
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DOI: https://doi.org/10.1038/nsmb1269
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