title: Toward a consensus on the binding specificity and promiscuity of PRC2 for RNA.
abstract: Polycomb repressive complex-2 (PRC2) is a histone methyltransferase required for epigenetic silencing during development and cancer. Early works suggested binding specificity of PRC2 to certain long non-coding RNAs for recruitment to chromatin. More recent studies provided evidence both in favor and against this idea. Here, we bridge the two existing models of PRC2-RNA interaction. RepA RNA is a good binding partner for PRC2, while multiple non-relevant RNAs, including bacterial mRNAs, also bind PRC2; Kds depend to some extent on the experimental conditions. Human and mouse PRC2 have broadly similar RNA-binding properties in vitro. Examination of evidence supporting an existing model for site-specific recruitment of PRC2 by a well-defined RNA motif in cells reveals that results are PRC2 independent. We conclude that promiscuous and specific RNA-binding activities of PRC2 in vitro are not mutually exclusive, and that binding specificity in vivo remains to be demonstrated.
authors.affiliation: Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, BioFrontiers Institute, University of Colorado, Boulder, CO 80309, USA.
authors.forename: Chen
authors.initials: C
authors.lastname: Davidovich
authors.affiliation: Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, BioFrontiers Institute, University of Colorado, Boulder, CO 80309, USA.
authors.forename: Xueyin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Howard Hughes Medical Institute, Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Catherine
authors.initials: C
authors.lastname: Cifuentes-Rojas
authors.affiliation: Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, BioFrontiers Institute, University of Colorado, Boulder, CO 80309, USA.
authors.forename: Karen J
authors.initials: KJ
authors.lastname: Goodrich
authors.affiliation: Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, BioFrontiers Institute, University of Colorado, Boulder, CO 80309, USA.
authors.forename: Anne R
authors.initials: AR
authors.lastname: Gooding
authors.affiliation: Howard Hughes Medical Institute, Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA. Electronic address: lee@molbio.mgh.harvard.edu.
authors.forename: Jeannie T
authors.initials: JT
authors.lastname: Lee
authors.affiliation: Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, BioFrontiers Institute, University of Colorado, Boulder, CO 80309, USA. Electronic address: thomas.cech@colorado.edu.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Cech
mesh_terms: D000818:Animals; D057809:HEK293 Cells; D006801:Humans; D066298:In Vitro Techniques; D055029:Inverted Repeat Sequences; D051379:Mice; D063151:Polycomb Repressive Complex 2 / Q000378:metabolism*; D011485:Protein Binding; D012313:RNA / Q000737:chemistry / Q000378:metabolism*; D062085:RNA, Long Noncoding / Q000378:metabolism
chemical_list: D062085:RNA, Long Noncoding; D012313:RNA; D063151:Polycomb Repressive Complex 2