Toward a consensus on the binding specificity and promiscuity of PRC2 for RNA

Mol Cell. 2015 Feb 5;57(3):552-8. doi: 10.1016/j.molcel.2014.12.017. Epub 2015 Jan 15.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • HEK293 Cells
  • Humans
  • In Vitro Techniques
  • Inverted Repeat Sequences
  • Mice
  • Polycomb Repressive Complex 2 / metabolism*
  • Protein Binding*
  • RNA / chemistry
  • RNA / metabolism*
  • RNA, Long Noncoding / metabolism


  • RNA, Long Noncoding
  • RNA
  • Polycomb Repressive Complex 2