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Exploring Sequence Space to Identify Binding Sites for Regulatory RNA-Binding Proteins
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Cryptic RNA-binding by PRC2 components EZH2 and SUZ12.

Juan G Betancur1,2,3, Yukihide Tomari1,2

  • 1a Institute of Molecular and Cellular Biosciences; The University of Tokyo ; Bunkyo-ku, Tokyo , Japan.

RNA Biology
|July 16, 2015
PubMed
Summary

Polycomb repressive complex 2 (PRC2) directly binds RNA via its EZH2 and SUZ12 subunits. This RNA-binding activity, particularly with longer RNAs, may influence PRC2 recruitment, though substrate preference remains complex.

Keywords:
EZH2HOTAIRPRC2SUZ12XistlncRNA

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Area of Science:

  • Epigenetics and Chromatin Biology
  • Molecular Biology
  • RNA Biology

Background:

  • Polycomb repressive complex 2 (PRC2) epigenetically silences genes by modifying histone H3 lysine 27 (H3K27me2/3).
  • The precise mechanisms for recruiting PRC2 to specific genomic loci are not fully understood.
  • Long non-coding RNAs (lncRNAs) are proposed as potential guides for PRC2 targeting.

Purpose of the Study:

  • To investigate the direct RNA-binding capabilities of individual PRC2 components.
  • To explore the role of RNA binding in PRC2 recruitment and function.
  • To characterize the substrate specificity of PRC2's RNA-binding activity.

Main Methods:

  • Purification of individual PRC2 subunits from human cultured cells.
  • In vitro biochemical assays to assess RNA binding by EZH2 and SUZ12.
  • Analysis of RNA length and sequence in relation to PRC2 subunit binding affinity.

Main Results:

  • EZH2 and SUZ12 subunits of PRC2 were found to directly bind to RNA.
  • A preference for longer RNA molecules was observed for these PRC2 subunits.
  • RNA length alone was insufficient to fully explain the substrate specificity of PRC2's RNA binding.

Conclusions:

  • PRC2 subunits EZH2 and SUZ12 possess intrinsic RNA-binding activity.
  • RNA binding by PRC2 components may contribute to locus-specific recruitment.
  • Further research is needed to fully elucidate the complexities of PRC2-RNA interactions and substrate selection.