SIRT7-dependent deacetylation of the U3-55k protein controls pre-rRNA processing.
SIRT7-dependent deacetylation of the U3-55k protein controls pre-rRNA processing.
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DOI：
10.1038/ncomms10734
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发表时间：
2016-02-12
影响因子：
16.6
通讯作者：
Voit R
中科院分区：
文献类型：
--
作者：
Chen S;Blank MF;Iyer A;Huang B;Wang L;Grummt I;Voit R
SIRT7是一种依赖NAD+的蛋白去乙酰基酶，在核糖体的生物发生和细胞增殖中具有重要作用。以往的研究证实，SIRT7与RNA聚合酶I有关，与核糖体前RNA相互作用，促进rRNA合成。在这里，我们发现SIRT7也与小核仁RNP(SnoRNP)有关，snoRNP参与了前rRNA的加工和rRNA的成熟。SIRT7的敲除会损害U3 snoRNA依赖的早期切割步骤，这是产生18S rRNA所必需的。从机制上讲，SIRT7对U3 snoRNP复合体的核心成分U3-55k进行脱乙酰化，U3-55k的可逆乙酰化调节U3-55k与U3 snoRNA的结合。SIRT7的脱乙酰基增强了U3-55k与U3 snoRNA的结合，这是Pre-rRNA加工的先决条件。在应激条件下，SIRT7从核仁中释放，导致U3-55k的超乙酰化和前rRNA加工的减弱。结果揭示了SIRT7在核糖体生物发生中的多方面作用，调节rRNA的转录和加工。SIRT7是一种蛋白质脱乙酰酶，在rRNA合成、核糖体生物发生和细胞增殖中具有重要作用。在这里，作者展示了SIRT7通过U3 snoRNP复合体的核心成分U3-55k的脱乙酰基在rRNA成熟中的作用。
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. SIRT7 is a protein deacetylase with important roles in rRNA synthesis, ribosome biogenesis and cell proliferation. Here the authors show a role of SIRT7 in rRNA maturation via deacetylation of U3-55k, a core component of the U3 snoRNP complex.