title: Destabilization of B2 RNA by EZH2 Activates the Stress Response.
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.
authors.affiliation: 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.
authors.forename: Athanasios
authors.initials: A
authors.lastname: Zovoilis
authors.affiliation: 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.
authors.forename: Catherine
authors.initials: C
authors.lastname: Cifuentes-Rojas
authors.affiliation: 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.
authors.forename: Hsueh-Ping
authors.initials: HP
authors.lastname: Chu
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Alfredo J
authors.initials: AJ
authors.lastname: Hernandez
authors.affiliation: 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.
authors.forename: Jeannie T
authors.initials: JT
authors.lastname: Lee
mesh_terms: D000818:Animals; D053595:Embryonic Stem Cells / Q000378:metabolism; D000071221:Enhancer of Zeste Homolog 2 Protein / Q000378:metabolism*; D005786:Gene Expression Regulation; D018869:Heat-Shock Response; D051379:Mice; D041681:NIH 3T3 Cells; D012319:RNA Polymerase II / Q000378:metabolism; D022661:RNA, Untranslated / Q000378:metabolism*; D018626:Retroelements; D014158:Transcription, Genetic
chemical_list: D022661:RNA, Untranslated; D018626:Retroelements; D000071221:Enhancer of Zeste Homolog 2 Protein; C498410:Ezh2 protein, mouse; D012319:RNA Polymerase II
keywords: B2 RNA; EZH2; RNA cleavage; SINE; heat shock; polycomb; stress; transcription