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SIRT7-dependent deacetylation of the U3-55k protein controls pre-rRNA processing

Author

Listed:
  • Sifan Chen

    (German Cancer Research Center, DKFZ-ZMBH Alliance, Im Neuenheimer Fed 581, 69120 Heidelberg, Germany)

  • Maximilian Felix Blank

    (German Cancer Research Center, DKFZ-ZMBH Alliance, Im Neuenheimer Fed 581, 69120 Heidelberg, Germany)

  • Aishwarya Iyer

    (German Cancer Research Center, DKFZ-ZMBH Alliance, Im Neuenheimer Fed 581, 69120 Heidelberg, Germany)

  • Bingding Huang

    (German Cancer Research Center
    Present address: NEO New Oncology AG, Gottfried-Hagenstraße 20, 51105 Cologne, Germany.)

  • Lin Wang

    (Genomics and Proteomics Core Facility, German Cancer Research Center)

  • Ingrid Grummt

    (German Cancer Research Center, DKFZ-ZMBH Alliance, Im Neuenheimer Fed 581, 69120 Heidelberg, Germany)

  • Renate Voit

    (German Cancer Research Center, DKFZ-ZMBH Alliance, Im Neuenheimer Fed 581, 69120 Heidelberg, Germany)

Abstract

SIRT7 is an NAD+-dependent protein deacetylase with important roles in ribosome biogenesis and cell proliferation. Previous studies have established that SIRT7 is associated with RNA polymerase I, interacts with pre-ribosomal RNA (rRNA) and promotes rRNA synthesis. Here we show that SIRT7 is also associated with small nucleolar RNP (snoRNPs) that are involved in pre-rRNA processing and rRNA maturation. Knockdown of SIRT7 impairs U3 snoRNA dependent early cleavage steps that are necessary for generation of 18S rRNA. Mechanistically, SIRT7 deacetylates U3-55k, a core component of the U3 snoRNP complex, and reversible acetylation of U3-55k modulates the association of U3-55k with U3 snoRNA. Deacetylation by SIRT7 enhances U3-55k binding to U3 snoRNA, which is a prerequisite for pre-rRNA processing. Under stress conditions, SIRT7 is released from nucleoli, leading to hyperacetylation of U3-55k and attenuation of pre-rRNA processing. The results reveal a multifaceted role of SIRT7 in ribosome biogenesis, regulating both transcription and processing of rRNA.

Suggested Citation

  • Sifan Chen & Maximilian Felix Blank & Aishwarya Iyer & Bingding Huang & Lin Wang & Ingrid Grummt & Renate Voit, 2016. "SIRT7-dependent deacetylation of the U3-55k protein controls pre-rRNA processing," Nature Communications, Nature, vol. 7(1), pages 1-11, April.
  • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10734
    DOI: 10.1038/ncomms10734
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