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

Sifan Chen,Renate Voit,Maximilian Felix Blank,Bingding Huang,Aishwarya Iyer,Ingrid Grummt,Lin Wang

doi:10.1038/ncomms10734

Sifan Chen, Renate Voit + Show 5 more

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https://doi.org/10.1038/ncomms10734

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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.

Highlights

SIRT7 is an NAD þ -dependent protein deacetylase with important roles in ribosome biogenesis and cell proliferation
Consistent with SIRT7 being associated with polymerase I (Pol I) and activating ribosomal DNA (rDNA) transcription[24], the majority of SIRT7-associated RNA reads (87.8%) covered the entire transcribed region of rDNA, supporting that SIRT7 binds to nascent pre-ribosomal RNA (rRNA) (Fig. 1a and Supplementary Fig. 1b,c)
About 9.7% of reads mapped to transcripts synthesized by Pol II and 0.8% to RNAs synthesized by Pol III

Summary

Introduction

SIRT7 is an NAD þ -dependent protein deacetylase with important roles in ribosome biogenesis and cell proliferation. Ribosome biogenesis is a highly regulated process that requires the coordinated activity of all three nuclear DNA-dependent RNA polymerases (Pol I, II and III) along with more than 200 trans-acting factors, including transcription factors, small nucleolar RNPs (snoRNPs), ribosomal proteins, and proteins that promote processing and modification of ribosomal RNA (rRNA)[1,2,3]. The 12S U3 snoRNP particle constitutes a subcomplex of the phylogenetically conserved 80S/2.2 MDa small-subunit (SSU) processome, a large ribonucleoprotein complex that assembles on nascent pre-rRNA and is indispensable for ribosome biogenesis[7,8,9,10]. The results uncover a SIRT7-dependent mechanism that links rDNA transcription to pre-rRNA processing, reinforcing the pivotal role of SIRT7 in ribosome biogenesis, cell metabolism and homeostasis

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