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Promiscuous RNA binding by Polycomb repressive complex 2

Chen Davidovich1, Leon Zheng, Karen J Goodrich

  • 11] Department of Chemistry & Biochemistry, Howard Hughes Medical Institute, University of Colorado Boulder, Boulder, Colorado, USA. [2] BioFrontiers Institute, University of Colorado Boulder, Boulder, Colorado, USA.

Nature Structural & Molecular Biology
|October 1, 2013
PubMed

Insights

Polycomb repressive complex 2 (PRC2) binds promiscuously to various RNAs, not just specific long noncoding RNAs (lncRNAs). This broad RNA binding helps PRC2 maintain epigenetic silencing by scanning for and re-engaging escaped genes.

Area of Science:

  • Epigenetics
  • Molecular Biology
  • Genetics

Background:

  • Polycomb repressive complex 2 (PRC2) is crucial for epigenetic gene silencing during development and in diseases like cancer.
  • Long noncoding RNAs (lncRNAs) are known to recruit PRC2 to specific genomic locations.
  • The broader role of RNA in maintaining the overall repressed chromatin state is not well understood.

Purpose of the Study:

  • To investigate the binding affinities of human PRC2 to different RNA molecules.
  • To determine the general role of RNA in the maintenance of repressed chromatin by PRC2.
  • To explore the mechanism by which PRC2 maintains gene silencing.

Main Methods:

  • Measurement of binding constants between human PRC2 and various RNA transcripts, including human lncRNAs, bacterial, and ciliate RNAs.
  • Assessment of PRC2 occupancy on active and repressed genes in vivo.
  • Analysis of RNA size dependency on PRC2 binding affinity.

Main Results:

  • Human PRC2 exhibits comparable binding affinities for targeted human lncRNAs and non-specific bacterial or ciliate transcripts.
  • PRC2 binding affinity to RNA is dependent on RNA size, with shorter RNAs showing lower affinity.
  • In vivo, PRC2 is primarily found on repressed genes, but also associates with active genes not under PRC2 regulation.

Conclusions:

  • PRC2's promiscuous binding to RNA transcripts facilitates scanning for and re-engaging genes that have escaped repression, thereby maintaining the silenced state.
  • RNA transcripts may act as decoys for PRC2, contributing to the dynamic regulation of chromatin.
  • This RNA-mediated scanning mechanism provides a general strategy for PRC2 to ensure stable epigenetic silencing.

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