Transcriptional repressor NIR functions in the ribosome RNA processing of both 40S and 60S subunits.
Transcriptional repressor NIR functions in the ribosome RNA processing of both 40S and 60S subunits.
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转录抑制子 NIR 在 40S 和 60S 亚基的核糖体 RNA 加工中发挥作用
DOI：
10.1371/journal.pone.0031692
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Ke Y
中科院分区：
文献类型：
--
作者：
Wu J;Zhang Y;Wang Y;Kong R;Hu L;Schuele R;Du X;Ke Y
背景NIR被鉴定为组蛋白乙酰转移酶的抑制剂，其抑制p53的转录激活。NIR主要定位于核仁中，称为Noc 2 p，其参与60 S核糖体亚基的成熟。然而，NIR在核仁中的功能仍然不确定。在核仁中，47 S核糖体RNA前体（pre-rRNA）被转录并加工成18 S、5.8S和28 S rRNA。18 S rRNA被整合到40 S核糖体亚基中，而28 S和5.8S rRNA被整合到60 S亚基中。U3小核仁RNA（snoRNA）指导18 S rRNA的加工，U8 snoRNA介导28 S和5.8 S rRNA的加工。核仁的功能性破坏通常导致p53激活以抑制细胞增殖。方法/主要发现Western印迹法显示NIR在不同的人类细胞系中普遍表达。通过脉冲追踪实验评估，通过siRNA敲低NIR导致18 S、28 S和5.8SrRNA的抑制。采用蔗糖梯度离心法从细胞核中分离出前体rRNA颗粒（pre-rRNP），对pre-RNP组分的分析表明，NIR存在于60 S和40 S亚基的pre-RNP中，并与60 S pre-rNP中的32 S和12 S pre-rRNA共分离。蛋白质-RNA结合实验表明，NIR与32 S pre-rRNA和U8 snoRNA相关。此外，NIR结合U3 snoRNA。这是一个新的发现，NIR的耗尽不影响p53蛋白水平，但去抑制p53的乙酰化和激活p21。结论我们首次提供了转录抑制因子在40 S和60 S亚基的rRNA生物合成中发挥作用的证据。我们的研究结果还表明，核仁蛋白可能通过影响p53修饰而不是影响p53蛋白水平来向p53传递信号。
Background NIR was identified as an inhibitor of histone acetyltransferase and it represses transcriptional activation of p53. NIR is predominantly localized in the nucleolus and known as Noc2p, which is involved in the maturation of the 60S ribosomal subunit. However, how NIR functions in the nucleolus remains undetermined. In the nucleolus, a 47S ribosomal RNA precursor (pre-rRNA) is transcribed and processed to produce 18S, 5.8S and 28S rRNAs. The 18S rRNA is incorporated into the 40S ribosomal subunit, whereas the 28S and 5.8S rRNAs are incorporated into the 60S subunit. U3 small nucleolar RNA (snoRNA) directs 18S rRNA processing and U8 snoRNA mediates processing of 28S and 5.8 S rRNAs. Functional disruption of nucleolus often causes p53 activation to inhibit cell proliferation. Methodology/Principal Findings Western blotting showed that NIR is ubiquitously expressed in different human cell lines. Knock-down of NIR by siRNA led to inhibition of the 18S, 28S and 5.8S rRNAs evaluated by pulse-chase experiment. Pre-rRNA particles (pre-rRNPs) were fractionated from the nucleus by sucrose gradient centrifugation and analysis of the pre-RNPs components showed that NIR existed in the pre-RNPs of both the 60S and 40S subunits and co-fractionated with 32S and 12S pre-rRNAs in the 60S pre-rRNP. Protein-RNA binding experiments demonstrated that NIR is associated with the 32S pre-rRNA and U8 snoRNA. In addition, NIR bound U3 snoRNA. It is a novel finding that depletion of NIR did not affect p53 protein level but de-repressed acetylation of p53 and activated p21. Conclusions We provide the first evidence for a transcriptional repressor to function in the rRNA biogenesis of both the 40S and 60S subunits. Our findings also suggested that a nucleolar protein may alternatively signal to p53 by affecting the p53 modification rather than affecting p53 protein level.
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影响因子：
14.9
作者：
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通讯作者：
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DOI：
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发表时间：
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期刊：
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影响因子：
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影响因子：
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