Targeting of Polycomb Repressive Complex 2 to RNA by Short Repeats of Consecutive Guanines

Xueyin Wang, Karen J Goodrich, Anne R Gooding, Haroon Naeem, Stuart Archer, Richard D. Paucek, Daniel T. Youmans, Thomas R Cech, Chen Davidovich

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Polycomb repressive complex 2 (PRC2) is a histone methyltransferase that trimethylates H3K27, a mark of repressed chromatin. Mammalian PRC2 binds RNA promiscuously, with thousands of target transcripts in vivo. But what does PRC2 recognize in these RNAs? Here we show that purified human PRC2 recognizes G > C,U ≫ A in single-stranded RNA and has a high affinity for folded guanine quadruplex (G4) structures but little binding to duplex RNAs. Importantly, G-tract motifs are significantly enriched among PRC2-binding transcripts in vivo. DNA sequences coding for PRC2-binding RNA motifs are enriched at PRC2-binding sites on chromatin and H3K27me3-modified nucleosomes. Collectively, the abundance of PRC2-binding RNA motifs rationalizes the promiscuous RNA binding of PRC2, and their enrichment at Polycomb target genes provides a means for RNA-mediated regulation.

Original languageEnglish
Pages (from-to)1056-1067
Number of pages12
JournalMolecular Cell
Volume65
Issue number6
DOIs
Publication statusPublished - 16 Mar 2017

Keywords

  • G-quadruplex
  • motif
  • Polycomb repressive complex 2
  • PRC2
  • promiscuous RNA binding
  • RNA binding specificity

Cite this

Wang, Xueyin ; Goodrich, Karen J ; Gooding, Anne R ; Naeem, Haroon ; Archer, Stuart ; Paucek, Richard D. ; Youmans, Daniel T. ; Cech, Thomas R ; Davidovich, Chen. / Targeting of Polycomb Repressive Complex 2 to RNA by Short Repeats of Consecutive Guanines. In: Molecular Cell. 2017 ; Vol. 65, No. 6. pp. 1056-1067.
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abstract = "Polycomb repressive complex 2 (PRC2) is a histone methyltransferase that trimethylates H3K27, a mark of repressed chromatin. Mammalian PRC2 binds RNA promiscuously, with thousands of target transcripts in vivo. But what does PRC2 recognize in these RNAs? Here we show that purified human PRC2 recognizes G > C,U ≫ A in single-stranded RNA and has a high affinity for folded guanine quadruplex (G4) structures but little binding to duplex RNAs. Importantly, G-tract motifs are significantly enriched among PRC2-binding transcripts in vivo. DNA sequences coding for PRC2-binding RNA motifs are enriched at PRC2-binding sites on chromatin and H3K27me3-modified nucleosomes. Collectively, the abundance of PRC2-binding RNA motifs rationalizes the promiscuous RNA binding of PRC2, and their enrichment at Polycomb target genes provides a means for RNA-mediated regulation.",
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Wang, X, Goodrich, KJ, Gooding, AR, Naeem, H, Archer, S, Paucek, RD, Youmans, DT, Cech, TR & Davidovich, C 2017, 'Targeting of Polycomb Repressive Complex 2 to RNA by Short Repeats of Consecutive Guanines' Molecular Cell, vol. 65, no. 6, pp. 1056-1067. https://doi.org/10.1016/j.molcel.2017.02.003

Targeting of Polycomb Repressive Complex 2 to RNA by Short Repeats of Consecutive Guanines. / Wang, Xueyin; Goodrich, Karen J; Gooding, Anne R; Naeem, Haroon; Archer, Stuart; Paucek, Richard D.; Youmans, Daniel T.; Cech, Thomas R; Davidovich, Chen.

In: Molecular Cell, Vol. 65, No. 6, 16.03.2017, p. 1056-1067.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Wang, Xueyin

AU - Goodrich, Karen J

AU - Gooding, Anne R

AU - Naeem, Haroon

AU - Archer, Stuart

AU - Paucek, Richard D.

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AU - Cech, Thomas R

AU - Davidovich, Chen

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AB - Polycomb repressive complex 2 (PRC2) is a histone methyltransferase that trimethylates H3K27, a mark of repressed chromatin. Mammalian PRC2 binds RNA promiscuously, with thousands of target transcripts in vivo. But what does PRC2 recognize in these RNAs? Here we show that purified human PRC2 recognizes G > C,U ≫ A in single-stranded RNA and has a high affinity for folded guanine quadruplex (G4) structures but little binding to duplex RNAs. Importantly, G-tract motifs are significantly enriched among PRC2-binding transcripts in vivo. DNA sequences coding for PRC2-binding RNA motifs are enriched at PRC2-binding sites on chromatin and H3K27me3-modified nucleosomes. Collectively, the abundance of PRC2-binding RNA motifs rationalizes the promiscuous RNA binding of PRC2, and their enrichment at Polycomb target genes provides a means for RNA-mediated regulation.

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Wang X, Goodrich KJ, Gooding AR, Naeem H, Archer S, Paucek RD et al. Targeting of Polycomb Repressive Complex 2 to RNA by Short Repeats of Consecutive Guanines. Molecular Cell. 2017 Mar 16;65(6):1056-1067. https://doi.org/10.1016/j.molcel.2017.02.003