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

doi:10.1016/j.molcel.2017.02.003

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

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

Authors

Xueyin Wang¹, Karen J Goodrich¹, Anne R Gooding¹, Haroon Naeem², Stuart Archer², Richard D Paucek¹, Daniel T Youmans³, Thomas R Cech⁴, Chen Davidovich⁵

Affiliations

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: [email protected].
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: [email protected].

PMID: 28306504
DOI: 10.1016/j.molcel.2017.02.003

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.

MeSH terms

Binding Sites
Chromatin / chemistry
Chromatin / enzymology*
Chromatin / genetics
Enhancer of Zeste Homolog 2 Protein / genetics
Enhancer of Zeste Homolog 2 Protein / metabolism
Gene Expression Regulation
Guanine / metabolism*
HEK293 Cells
Humans
Nucleic Acid Conformation
Nucleosomes / chemistry
Nucleosomes / enzymology*
Nucleosomes / genetics
Nucleotide Motifs
Polycomb Repressive Complex 2 / genetics
Polycomb Repressive Complex 2 / metabolism*
Protein Binding
RNA / chemistry
RNA / genetics
RNA / metabolism*
Structure-Activity Relationship
Transfection

Substances

Chromatin
Nucleosomes
Guanine
RNA
EZH2 protein, human
Enhancer of Zeste Homolog 2 Protein
Polycomb Repressive Complex 2