Research group leader: PD Dr. Renate Voit

Sirtuins: Regulators of cellular homeostasis

The mammalian Sirtuin protein family.

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. SIRT1 represses Pol I transcription during mitosis 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 transcription initiation complex formation (Voit et al 2015).

SIRT7 - a nuclear Sirtuin that adapts gene expression to cellular stress

The acetylation/deacetylation switch of PAF53 regulates rDNA transcription under stress
© Cell Press

SIRT7 expression correlates with cell growth and proliferation, being abundant in metabolically active cells and upregulated in cancer cells, but low or even absent in non-proliferating cells. We deciphered the molecular mechnisms underlying activation of RNA polymerase I (Pol I) transcription by SIRT7 showing that SIRT7 deacetylates PAF53, a subunit of Pol I. Hypoacetylation of PAF53 facilitates the association of PAF53/Pol I with rDNA upregulating transcriptional activity. Downregulation of Pol I transcription in response to different stress stimuli leads to release of SIRT7 from nucleoli and hyperacetylation of PAF53 (Ford et al 2006; Chen et al 2013). We are currently investigating the role of SIRT7 in cell proliferation and cellular stress as part of a signaling network that adapts RNA metabolism, global trasncription and ribosomal biogenesis to the metabolic state of normal and cancer cells. This work includes

  • genome-wide analysis of SIRT7 associated RNAs (CLIP-seq)
  • ChIP-seq to identify SIRT7 occupied genomic loci
  • proteomic approaches to identify interaction partners of SIRT7
  • regulation of SIRT7 activity by signaling pathways
  • SIRT7 gain- and loss-of-function studies

People currently involved in these projects:

Renate Voit, Sifan Chen, Aishwarya Iyer, Maximilian Blank, Chenlin Song, Jeanette Seiler, Horace Chan

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