title: Heat shock represses rRNA synthesis by inactivation of TIF-IA and lncRNA-dependent changes in nucleosome positioning.
abstract: Attenuation of ribosome biogenesis in suboptimal growth environments is crucial for cellular homeostasis and genetic integrity. Here, we show that shutdown of rRNA synthesis in response to elevated temperature is brought about by mechanisms that target both the RNA polymerase I (Pol I) transcription machinery and the epigenetic signature of the rDNA promoter. Upon heat shock, the basal transcription factor TIF-IA is inactivated by inhibition of CK2-dependent phosphorylations at Ser170/172. Attenuation of pre-rRNA synthesis in response to heat stress is accompanied by upregulation of PAPAS, a long non-coding RNA (lncRNA) that is transcribed in antisense orientation to pre-rRNA. PAPAS interacts with CHD4, the adenosine triphosphatase subunit of NuRD, leading to deacetylation of histones and movement of the promoter-bound nucleosome into a position that is refractory to transcription initiation. The results exemplify how stress-induced inactivation of TIF-IA and lncRNA-dependent changes of chromatin structure ensure repression of rRNA synthesis in response to thermo-stress.
authors.affiliation: Division of Molecular Biology of the Cell II, German Cancer Research Center, DKFZ-ZMBH Alliance, D-69120 Heidelberg, Germany.
authors.forename: Zhongliang
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Division of Molecular Biology of the Cell II, German Cancer Research Center, DKFZ-ZMBH Alliance, D-69120 Heidelberg, Germany.
authors.forename: Marcel A
authors.initials: MA
authors.lastname: Dammert
authors.affiliation: Division of Molecular Biology of the Cell II, German Cancer Research Center, DKFZ-ZMBH Alliance, D-69120 Heidelberg, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Hoppe
authors.affiliation: Division of Molecular Biology of the Cell II, German Cancer Research Center, DKFZ-ZMBH Alliance, D-69120 Heidelberg, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Bierhoff
authors.affiliation: Division of Molecular Biology of the Cell II, German Cancer Research Center, DKFZ-ZMBH Alliance, D-69120 Heidelberg, Germany i.grummt@dkfz.de.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Grummt
mesh_terms: D000818:Animals; D047390:Casein Kinase II / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly; D057809:HEK293 Cells; D018869:Heat-Shock Response / Q000235:genetics*; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex / Q000378:metabolism; D051379:Mice; D041681:NIH 3T3 Cells; D009707:Nucleosomes / Q000378:metabolism*; D010766:Phosphorylation; D035463:Pol1 Transcription Initiation Complex Proteins / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D062085:RNA, Long Noncoding / Q000378:metabolism*; D012335:RNA, Ribosomal / Q000096:biosynthesis*; D014158:Transcription, Genetic
chemical_list: D009707:Nucleosomes; D035463:Pol1 Transcription Initiation Complex Proteins; D062085:RNA, Long Noncoding; D012335:RNA, Ribosomal; C491074:Rrn3 protein, mouse; C000620155:long non-coding RNA PAPAS, mouse; D011495:Histone-Lysine N-Methyltransferase; D047390:Casein Kinase II; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex