Mammalian Sir2 homolog SIRT7 is an activator of RNA polymerase I transcription

  1. Ethan Ford1,3,
  2. Renate Voit2,3,
  3. Gregory Liszt1,
  4. Cornelia Magin2,
  5. Ingrid Grummt2, and
  6. Leonard Guarente1,4
  1. 1 Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA;
  2. 2 Department of Molecular Biology of the Cell II, German Cancer Research Center, Heidelberg D-69120, Germany
  1. 3

    ↵3 These authors contributed equally to this work.

Abstract

We investigated the role of SIRT7, one of the seven members of the mammalian sirtuin family. We show that SIRT7 is a widely expressed nucleolar protein that is associated with active rRNA genes (rDNA), where it interacts with RNA polymerase I (Pol I) as well as with histones. Overexpression of SIRT7 increases Pol I-mediated transcription, whereas knockdown of SIRT7 or inhibition of the catalytic activity results in decreased association of Pol I with rDNA and a reduction of Pol I transcription. Depletion of SIRT7 stops cell proliferation and triggers apoptosis. Our findings suggest that SIRT7 is a positive regulator of Pol I transcription and is required for cell viability in mammals.

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  1. Published in Advance April 17, 2006, doi: 10.1101/gad.1399706 Genes & Dev. 20: 1075-1080 Copyright © 2006, Cold Spring Harbor Laboratory Press

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