Mammalian Sir2 homolog SIRT7 is an activator of RNA polymerase I transcription.
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.
Ford
Ethan
E
Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Voit
Renate
R
Liszt
Gregory
G
Magin
Cornelia
C
Grummt
Ingrid
I
Guarente
Leonard
L
D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D049109:Cell Proliferation; D002470:Cell Survival; D004275:DNA, Ribosomal / Q000235:genetics / Q000378:metabolism; D020459:Genes, rRNA; D006657:Histones / Q000378:metabolism; D006801:Humans; D051379:Mice; D034622:RNA Interference; D012318:RNA Polymerase I / Q000235:genetics / Q000378:metabolism*; D037761:Sirtuins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation
D004275:DNA, Ribosomal; D006657:Histones; D012318:RNA Polymerase I; D037761:Sirtuins