title: SIRT7-dependent deacetylation of the U3-55k protein controls pre-rRNA processing.
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.
authors: Division of Molecular Biology of the Cell II, German Cancer Research Center, DKFZ-ZMBH Alliance, Im Neuenheimer Fed 581, 69120 Heidelberg, Germany.
authors: Sifan
authors: S
authors: Chen
authors: Division of Molecular Biology of the Cell II, German Cancer Research Center, DKFZ-ZMBH Alliance, Im Neuenheimer Fed 581, 69120 Heidelberg, Germany.
authors: Maximilian Felix
authors: MF
authors: Blank
authors: Division of Molecular Biology of the Cell II, German Cancer Research Center, DKFZ-ZMBH Alliance, Im Neuenheimer Fed 581, 69120 Heidelberg, Germany.
authors: Aishwarya
authors: A
authors: Iyer
authors: Division of Theoretical Bioinformatics, German Cancer Research Center, 69120 Heidelberg, Germany.
authors: Bingding
authors: B
authors: Huang
authors: Genomics and Proteomics Core Facility, German Cancer Research Center, 69120 Heidelberg, Germany.
authors: Lin
authors: L
authors: Wang
authors: Division of Molecular Biology of the Cell II, German Cancer Research Center, DKFZ-ZMBH Alliance, Im Neuenheimer Fed 581, 69120 Heidelberg, Germany.
authors: Ingrid
authors: I
authors: Grummt
authors: Division of Molecular Biology of the Cell II, German Cancer Research Center, DKFZ-ZMBH Alliance, Im Neuenheimer Fed 581, 69120 Heidelberg, Germany.
authors: Renate
authors: R
authors: Voit
mesh_terms: D015152:Blotting, Northern; D015153:Blotting, Western; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D005455:Fluorescent Antibody Technique; D055785:Gene Knockdown Techniques; D055786:Gene Knockout Techniques; D057809:HEK293 Cells; D006801:Humans; D047468:Immunoprecipitation; D066298:In Vitro Techniques; D012322:RNA Precursors / Q000378:metabolism*; D012323:RNA Processing, Post-Transcriptional / Q000235:genetics*; D012337:RNA, Ribosomal, 18S / Q000378:metabolism*; D020537:RNA, Small Nucleolar / Q000378:metabolism*; D020718:Ribonucleoproteins, Small Nucleolar / Q000378:metabolism*; D037761:Sirtuins / Q000235:genetics*
chemical_list: D012322:RNA Precursors; D012337:RNA, Ribosomal, 18S; D020537:RNA, Small Nucleolar; D020718:Ribonucleoproteins, Small Nucleolar; C510661:SIRT7 protein, human; C117377:ribonucleoprotein, U3 small nucleolar; D037761:Sirtuins