Repression of RNA polymerase I upon stress is caused by inhibition of RNA-dependent deacetylation of PAF53 by SIRT7

Mol Cell. 2013 Nov 7;52(3):303-13. doi: 10.1016/j.molcel.2013.10.010.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • CREB-Binding Protein / metabolism
  • HEK293 Cells
  • Humans
  • Lysine / genetics
  • RNA Polymerase I / antagonists & inhibitors
  • RNA Polymerase I / genetics*
  • RNA Precursors / metabolism
  • Sirtuins / genetics
  • Sirtuins / metabolism*
  • Stress, Physiological / genetics
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcriptional Activation / genetics*

Substances

  • POLR1E protein, human
  • RNA Precursors
  • SIRT7 protein, human
  • Transcription Factors
  • CREB-Binding Protein
  • CREBBP protein, human
  • RNA Polymerase I
  • Sirtuins
  • Lysine