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Mol Cell. 2017 Mar 16;65(6):1056-1067.e5. doi: 10.1016/j.molcel.2017.02.003.

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

Author information

1
Department of Chemistry & Biochemistry, BioFrontiers Institute and Howard Hughes Medical Institute, University of Colorado, Boulder, Boulder, CO 80309, USA.
2
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.
3
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.
4
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.
5
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.

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.

KEYWORDS:

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

PMID:
28306504
DOI:
10.1016/j.molcel.2017.02.003
[Indexed for MEDLINE]
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