title: Targeting of Polycomb Repressive Complex 2 to RNA by Short Repeats of Consecutive Guanines.
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.
authors.affiliation: Department of Chemistry & Biochemistry, BioFrontiers Institute and Howard Hughes Medical Institute, University of Colorado, Boulder, Boulder, CO 80309, USA.
authors.forename: Xueyin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Chemistry & Biochemistry, BioFrontiers Institute and Howard Hughes Medical Institute, University of Colorado, Boulder, Boulder, CO 80309, USA.
authors.forename: Karen J
authors.initials: KJ
authors.lastname: Goodrich
authors.affiliation: Department of Chemistry & Biochemistry, BioFrontiers Institute and Howard Hughes Medical Institute, University of Colorado, Boulder, Boulder, CO 80309, USA.
authors.forename: Anne R
authors.initials: AR
authors.lastname: Gooding
authors.affiliation: Monash Bioinformatics Platform, Monash University, Clayton, VIC 3800, Australia; Biomedicine Discovery Institute, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, VIC 3800, Australia.
authors.forename: Haroon
authors.initials: H
authors.lastname: Naeem
authors.affiliation: Monash Bioinformatics Platform, Monash University, Clayton, VIC 3800, Australia; Biomedicine Discovery Institute, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, VIC 3800, Australia.
authors.forename: Stuart
authors.initials: S
authors.lastname: Archer
authors.affiliation: Department of Chemistry & Biochemistry, BioFrontiers Institute and Howard Hughes Medical Institute, University of Colorado, Boulder, Boulder, CO 80309, USA.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Paucek
authors.affiliation: Department of Chemistry & Biochemistry, BioFrontiers Institute and Howard Hughes Medical Institute, University of Colorado, Boulder, Boulder, CO 80309, USA; University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Youmans
authors.affiliation: Department of Chemistry & Biochemistry, BioFrontiers Institute and Howard Hughes Medical Institute, University of Colorado, Boulder, Boulder, CO 80309, USA. Electronic address: thomas.cech@colorado.edu.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Cech
authors.affiliation: Biomedicine Discovery Institute, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, VIC 3800, Australia; Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia; EMBL-Australia and the ARC Centre of Excellence in Advanced Molecular Imaging, Clayton, VIC 3800, Australia. Electronic address: chen.davidovich@monash.edu.
authors.forename: Chen
authors.initials: C
authors.lastname: Davidovich
mesh_terms: D001665:Binding Sites; D002843:Chromatin / Q000737:chemistry / Q000201:enzymology* / Q000235:genetics; D000071221:Enhancer of Zeste Homolog 2 Protein / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006147:Guanine / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D009690:Nucleic Acid Conformation; D009707:Nucleosomes / Q000737:chemistry / Q000201:enzymology* / Q000235:genetics; D059372:Nucleotide Motifs; D063151:Polycomb Repressive Complex 2 / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D012313:RNA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014162:Transfection
chemical_list: D002843:Chromatin; D009707:Nucleosomes; D006147:Guanine; D012313:RNA; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2
keywords: G-quadruplex; PRC2; Polycomb repressive complex 2; RNA binding specificity; motif; promiscuous RNA binding