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

Yicheng Long, Ben Bolanos, Lihu Gong, Wei Liu, Karen J. Goodrich, Xin Yang, Siming Chen, Anne R. Gooding, Karen A. Maegley, Ketan S. Gajiwala, Alexei Brooun, Thomas R. Cech, Xin Liu

Research output: Contribution to journalArticle

11 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere31558
JournaleLife
Volume6
DOIs
StatePublished - Nov 29 2017

Fingerprint

Polycomb Repressive Complex 2
RNA
Amino Acids
Chaetomium
G-Quadruplexes
Deuterium
Missense Mutation
Epigenomics
Mutagenesis
Histones
Methylation
Lysine
Chromatin
Hydrogen
Mass Spectrometry
Proteins
Mass spectrometry
Crystal structure

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

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.

In: eLife, Vol. 6, e31558, 29.11.2017.

Research output: Contribution to journalArticle

Long, Y, Bolanos, B, Gong, L, Liu, W, Goodrich, KJ, Yang, X, Chen, S, Gooding, AR, Maegley, KA, Gajiwala, KS, Brooun, A, Cech, TR & Liu, X 2017, 'Conserved RNA-binding specificity of polycomb repressive complex 2 is achieved by dispersed amino acid patches in EZH2', eLife, vol. 6, e31558. https://doi.org/10.7554/eLife.31558
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. In: eLife. 2017 ; Vol. 6.
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AU - Gooding, Anne R.

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