title: Repression of RNA polymerase I upon stress is caused by inhibition of RNA-dependent deacetylation of PAF53 by SIRT7.
abstract: Sirtuins are NAD(+)-dependent protein deacetylases that connect metabolism and cellular homeostasis. Here we show that the nuclear Sirtuin SIRT7 targets PAF53, a subunit of RNA polymerase I (Pol I). Acetylation of PAF53 at lysine 373 by CBP and deacetylation by SIRT7 modulate the association of Pol I with DNA, hypoacetylation correlating with increased rDNA occupancy of Pol I and transcription activation. SIRT7 is released from nucleoli in response to different stress conditions, leading to hyperacetylation of PAF53 and decreased Pol I transcription. Nucleolar detention requires binding of SIRT7 to nascent pre-rRNA, linking the spatial distribution of SIRT7 and deacetylation of PAF53 to ongoing transcription. The results identify a nonhistone target of SIRT7 and uncover an RNA-mediated mechanism that adapts nucleolar transcription to stress signaling.
authors.affiliation: Division of Molecular Biology of the Cell II, German Cancer Research Center, DKFZ-ZMBH Alliance, D-69120 Heidelberg, Germany.
authors.forename: Sifan
authors.initials: S
authors.lastname: Chen
authors.forename: Jeanette
authors.initials: J
authors.lastname: Seiler
authors.forename: Magaly
authors.initials: M
authors.lastname: Santiago-Reichelt
authors.forename: Kerstin
authors.initials: K
authors.lastname: Felbel
authors.forename: Ingrid
authors.initials: I
authors.lastname: Grummt
authors.forename: Renate
authors.initials: R
authors.lastname: Voit
mesh_terms: D000107:Acetylation; D050882:CREB-Binding Protein / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D008239:Lysine / Q000235:genetics; D012318:RNA Polymerase I / Q000037:antagonists & inhibitors / Q000235:genetics*; D012322:RNA Precursors / Q000378:metabolism; D037761:Sirtuins / Q000235:genetics / Q000378:metabolism*; D013312:Stress, Physiological / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation / Q000235:genetics*
chemical_list: C099638:POLR1E protein, human; D012322:RNA Precursors; C510661:SIRT7 protein, human; D014157:Transcription Factors; D050882:CREB-Binding Protein; C494363:CREBBP protein, human; D012318:RNA Polymerase I; D037761:Sirtuins; D008239:Lysine