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Regulatory interactions between RNA and polycomb repressive complex 2

Catherine Cifuentes-Rojas1, Alfredo J Hernandez2, Kavitha Sarma1

  • 1Howard Hughes Medical Institute, Boston, MA 02114, USA; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.

Molecular Cell
|June 3, 2014
PubMed

Insights

Polycomb repressive complex 2 (PRC2) uses RNA to target genes. RNA inhibits PRC2 activity until JARID2 binding, revealing a novel regulatory mechanism for gene expression control.

Area of Science:

  • Epigenetics
  • Molecular Biology
  • Gene Regulation

Background:

  • Polycomb repressive complex 2 (PRC2) is crucial for gene silencing and implicated in diseases.
  • Recruitment mechanisms for PRC2 to target genes are not fully understood.
  • cis-regulatory RNA has been proposed as a key factor in PRC2 localization.

Purpose of the Study:

  • To biochemically and functionally investigate the interaction between PRC2 and RNA.
  • To elucidate the role of specific PRC2 subunits in RNA binding and recognition.
  • To understand how RNA influences PRC2's catalytic activity and chromatin targeting.

Main Methods:

  • Biochemical assays to measure RNA binding affinities of PRC2 subunits.
  • Functional studies using the X-inactivation model.
  • Enzymatic activity assays for PRC2 in the presence of RNA and JARID2.

Main Results:

  • PRC2 exhibits high discriminatory capabilities in RNA recognition.
  • EZH2 subunit shows the highest affinity for RNA, with EED modulating this interaction.
  • RNA binding is essential for targeting but inhibits EZH2's catalytic activity, which is relieved by JARID2.

Conclusions:

  • RNA acts as a guide for PRC2 to target genes.
  • JARID2 binding to chromatin-bound PRC2 is necessary to relieve RNA-mediated catalytic inhibition.
  • This study provides a molecular understanding of RNA-PRC2 interactions at the chromatin interface, impacting gene regulation insights.

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