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Senior Scientist: PD Dr. Renate Voit

Sirtuins are a family of NAD+-dependent protein deacetylases and ADP-ribosyltransferases involved in diverse cellular processes, such as cell cycle control, ageing, energy metabolism, and metabolic stress. Human cells express seven sirtuins, termed SIRT1-7, which serve distinct cellular functions. We found that SIRT1 and SIRT7 play an essential role in Pol I transcription. SIRT1 represses Pol I transcription by deacetylating TAFI68, an essential subunit of the Pol I-specific TBP-TAF complex SL1, thereby reversing PCAF-mediated acetylation of SL1, which is required for initiation complex formation.

SIRT7, on the other hand, is an activator of Pol I transcription. SIRT7 activates transcription by augmenting Pol I occupancy at the promoter and transcribed region. Knockdown of SIRT7 by siRNAs impairs rRNA synthesis and cell proliferation, and leads to apoptosis indicating that SIRT7 is essential for cell viability. We are currently investigating the link between SIRT1, SIRT7 and cell growth as part of a larger signaling network that adapts rDNA transcription and ribosome biogenesis to the metabolic state of the cells.