期刊论文详细信息
eLife
Conserved RNA-binding specificity of polycomb repressive complex 2 is achieved by dispersed amino acid patches in EZH2
Anne R Gooding1  Ketan S Gajiwala1  Wei Liu1  Karen A Maegley2  Siming Chen2  Lihu Gong2  Yicheng Long3  Xin Yang3  Alexei Brooun3  Thomas R Cech4  Karen J Goodrich5  Ben Bolanos5  Xin Liu5 
[1] Department of Biophysics, UT Southwestern Medical Center, Dallas, United States;Cecil H. and Ida Green Center for Reproductive Biology Sciences, Division of Basic Research, Department of Obstetrics and Gynecology, UT Southwestern Medical Center, Dallas, United States;Department of Chemistry and Biochemistry, BioFrontiers Institute, Howard Hughes Medical Institute, University of Colorado Boulder, Boulder, United States;Oncology Research Unit, Worldwide Research and Development, Pfizer Inc., San Diego, United States;Worldwide Medicinal Chemistry, Worldwide Research and Development, Pfizer Inc., San Diego, United States;
关键词: epigenetics;    PRC2;    RNA binding proteins;    G-quadruplex RNA;    HDX-MS;    Chaetomium thermophilum;   
DOI  :  10.7554/eLife.31558
来源: DOAJ
【 摘 要 】

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.

【 授权许可】

Unknown   

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