@article{5c18de632be1498fba42d6a874b0f048,
title = "Conserved RNA-binding specificity of polycomb repressive complex 2 is achieved by dispersed amino acid patches in EZH2",
abstract = "Polycomb repressive complex 2 (PRC2) is a key chromatin modifier responsible for methylation of lysine 27 in histone H3. PRC2 has been shown to interact with thousands of RNA species in vivo, but understanding the physiological function of RNA binding has been hampered by the lack of separation-of-function mutants. Here, we use comprehensive mutagenesis and hydrogen deuterium exchange mass spectrometry (HDX-MS) to identify critical residues for RNA interaction in PRC2 core complexes from Homo sapiens and Chaetomium thermophilum, for which crystal structures are known. Preferential binding of G-quadruplex RNA is conserved, surprisingly using different protein elements. Key RNA-binding residues are spread out along the surface of EZH2, with other subunits including EED also contributing, and missense mutations of some of these residues have been found in cancer patients. The unusual nature of this protein-RNA interaction provides a paradigm for other epigenetic modifiers that bind RNA without canonical RNA-binding motifs.",
author = "Yicheng Long and Ben Bolanos and Lihu Gong and Wei Liu and Goodrich, {Karen J.} and Xin Yang and Siming Chen and Gooding, {Anne R.} and Maegley, {Karen A.} and Gajiwala, {Ketan S.} and Alexei Brooun and Cech, {Thomas R.} and Xin Liu",
note = "Funding Information: We thank members of the Cech lab, Oncology Structural Biology and Protein Science group, and the Liu lab for useful conversations. We also thank Daniel T Youmans for technical advice and reagents for the RNA immunoprecipitation experiments. TRC is an investigator of the HHMI, which supported this research. This research was supported by Welch Foundation research grant I-1790, CPRIT research grant R1119, Rita Allen Foundation research grant, UT Southwestern Medical Center Endowed Scholar fund, and NIH grants GM114576 and GM121662 to XL XL is a W W Caruth, Jr. Scholar in Biomedical Research. This research also received support from the Cecil H and Ida Green Center Training Program in Reproductive Biology Sciences Research. Pfizer Alexei Brooun Howard Hughes Medical Institute Thomas R Cech Welch Foundation research grant I-1790 Xin Liu Cancer Prevention and Research Institute of Texas research grant R1119 Xin Liu Rita Allen Foundation Xin Liu National Institute of General Medical Sciences GM114576 Xin Liu National Institute of General Medical Sciences GM121662 Xin Liu University of Texas Southwestern Medical Center Endowed Scholar Fund Xin Liu The Cecil H. and Ida M. Green Center Xin Liu The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. Funding Information: We thank members of the Cech lab, Oncology Structural Biology and Protein Science group, and the Liu lab for useful conversations. We also thank Daniel T Youmans for technical advice and reagents for the RNA immunoprecipitation experiments. TRC is an investigator of the HHMI, which supported this research. This research was supported by Welch Foundation research grant I-1790, CPRIT research grant R1119, Rita Allen Foundation research grant, UT Southwestern Medical Center Endowed Scholar fund, and NIH grants GM114576 and GM121662 to XL XL is a W W Caruth, Jr. Scholar in Biomedical Research. This research also received support from the Cecil H and Ida Green Center Training Program in Reproductive Biology Sciences Research. Funding Information: research grant I-1790 Publisher Copyright: {\textcopyright} Long et al.",
year = "2017",
month = nov,
day = "29",
doi = "10.7554/eLife.31558",
language = "English (US)",
volume = "6",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications",
}