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Cell. 2016 Dec 15;167(7):1788-1802.e13. doi: 10.1016/j.cell.2016.11.041.

Destabilization of B2 RNA by EZH2 Activates the Stress Response.

Author information

1
Howard Hughes Medical Institute; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Genetics, Harvard Medical School, Boston, MA 02114, USA.
2
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
3
Howard Hughes Medical Institute; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Genetics, Harvard Medical School, Boston, MA 02114, USA. Electronic address: lee@molbio.mgh.harvard.edu.

Abstract

More than 98% of the mammalian genome is noncoding, and interspersed transposable elements account for ∼50% of noncoding space. Here, we demonstrate that a specific interaction between the polycomb protein EZH2 and RNA made from B2 SINE retrotransposons controls stress-responsive genes in mouse cells. In the heat-shock model, B2 RNA binds stress genes and suppresses their transcription. Upon stress, EZH2 is recruited and triggers cleavage of B2 RNA. B2 degradation in turn upregulates stress genes. Evidence indicates that B2 RNA operates as a "speed bump" against advancement of RNA polymerase II, and temperature stress releases the brakes on transcriptional elongation. These data attribute a new function to EZH2 that is independent of its histone methyltransferase activity and reconcile how EZH2 can be associated with both gene repression and activation. Our study reveals that EZH2 and B2 together control activation of a large network of genes involved in thermal stress.

KEYWORDS:

B2 RNA; EZH2; RNA cleavage; SINE; heat shock; polycomb; stress; transcription

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PMID:
27984727
PMCID:
PMC5552366
DOI:
10.1016/j.cell.2016.11.041
[Indexed for MEDLINE]
Free PMC Article

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