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Conserved RNA-binding specificity of polycomb repressive complex 2 is achieved by dispersed amino acid patches in EZH2

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-f...

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Autores principales: Long, Yicheng, Bolanos, Ben, Gong, Lihu, Liu, Wei, Goodrich, Karen J, Yang, Xin, Chen, Siming, Gooding, Anne R, Maegley, Karen A, Gajiwala, Ketan S, Brooun, Alexei, Cech, Thomas R, Liu, Xin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5706960/
https://www.ncbi.nlm.nih.gov/pubmed/29185984
http://dx.doi.org/10.7554/eLife.31558
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author Long, Yicheng
Bolanos, Ben
Gong, Lihu
Liu, Wei
Goodrich, Karen J
Yang, Xin
Chen, Siming
Gooding, Anne R
Maegley, Karen A
Gajiwala, Ketan S
Brooun, Alexei
Cech, Thomas R
Liu, Xin
author_facet Long, Yicheng
Bolanos, Ben
Gong, Lihu
Liu, Wei
Goodrich, Karen J
Yang, Xin
Chen, Siming
Gooding, Anne R
Maegley, Karen A
Gajiwala, Ketan S
Brooun, Alexei
Cech, Thomas R
Liu, Xin
author_sort Long, Yicheng
collection PubMed
description 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.
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spelling pubmed-57069602017-11-30 Conserved RNA-binding specificity of polycomb repressive complex 2 is achieved by dispersed amino acid patches in EZH2 Long, Yicheng Bolanos, Ben Gong, Lihu Liu, Wei Goodrich, Karen J Yang, Xin Chen, Siming Gooding, Anne R Maegley, Karen A Gajiwala, Ketan S Brooun, Alexei Cech, Thomas R Liu, Xin eLife Biochemistry and Chemical Biology 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. eLife Sciences Publications, Ltd 2017-11-29 /pmc/articles/PMC5706960/ /pubmed/29185984 http://dx.doi.org/10.7554/eLife.31558 Text en © 2017, Long et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Biochemistry and Chemical Biology
Long, Yicheng
Bolanos, Ben
Gong, Lihu
Liu, Wei
Goodrich, Karen J
Yang, Xin
Chen, Siming
Gooding, Anne R
Maegley, Karen A
Gajiwala, Ketan S
Brooun, Alexei
Cech, Thomas R
Liu, Xin
Conserved RNA-binding specificity of polycomb repressive complex 2 is achieved by dispersed amino acid patches in EZH2
title Conserved RNA-binding specificity of polycomb repressive complex 2 is achieved by dispersed amino acid patches in EZH2
title_full Conserved RNA-binding specificity of polycomb repressive complex 2 is achieved by dispersed amino acid patches in EZH2
title_fullStr Conserved RNA-binding specificity of polycomb repressive complex 2 is achieved by dispersed amino acid patches in EZH2
title_full_unstemmed Conserved RNA-binding specificity of polycomb repressive complex 2 is achieved by dispersed amino acid patches in EZH2
title_short Conserved RNA-binding specificity of polycomb repressive complex 2 is achieved by dispersed amino acid patches in EZH2
title_sort conserved rna-binding specificity of polycomb repressive complex 2 is achieved by dispersed amino acid patches in ezh2
topic Biochemistry and Chemical Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5706960/
https://www.ncbi.nlm.nih.gov/pubmed/29185984
http://dx.doi.org/10.7554/eLife.31558
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