1A6/DRIM, a novel t-UTP, activates RNA polymerase I transcription and promotes cell proliferation.
1A6/DRIM, a novel t-UTP, activates RNA polymerase I transcription and promotes cell proliferation.
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1A6/DRIM 是一种新型 t-UTP，可激活 RNA 聚合酶 I 转录并促进细胞增殖。
DOI：
10.1371/journal.pone.0014244
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发表时间：
2010-12-07
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：
Peng Q;Wu J;Zhang Y;Liu Y;Kong R;Hu L;Du X;Ke Y
核糖体生物合成是蛋白质合成和细胞增殖所必需的。核糖体亚基在47 S核糖体RNA前体通过RNA聚合酶I转录和rRNA加工后组装在核仁中，以产生成熟的18 S、28 S和5.8S rRNA。18 S rRNA被掺入核糖体小亚基，而28 S和5.8S rRNA被掺入核糖体大亚基。Pol I转录和rRNA加工是协调的过程，并且这种协调已被证明是由称为t-UTPs的U3蛋白亚组介导的。迄今为止，已经在人体中鉴定出五种t-UTP，但是在t-UTP激活Pol I中起作用的机制仍然未知。在这项研究中，我们已经确定了1A 6/DRIM，这是确定为UTP 20在我们以前的研究，作为一个t-UTP。本研究探讨了1A 6/DRIM在Pol I转录中的功能和作用机制。通过北方印迹法测定，siRNA敲低1A 6/DRIM导致47 S pre-rRNA水平降低。用荧光素酶报告基因评估，1A 6/DRIM的异位表达被激活并且1A 6/DRIM的敲低抑制人rDNA启动子。染色质免疫沉淀（ChIP）实验表明1A 6/DRIM结合UBF和rDNA启动子。Re-ChIP分析表明1A 6/DRIM与UBF在rDNA启动子处相互作用。免疫沉淀证实了1A 6/DRIM与核仁乙酰转移酶hALP之间的相互作用。值得注意的是，敲低1A 6/DRIM显著抑制UBF乙酰化。有意义的发现是，1A 6/DRIM缺失作为一种核仁应激，引起p53水平升高，并通过将细胞阻滞在G1期来抑制细胞增殖。我们确定1A 6/DRIM是一种新的t-UTP。我们的研究结果表明，1A 6/DRIM激活Pol I转录最有可能通过与hALP和UBF结合，从而影响UBF的乙酰化。
Ribosome biogenesis is required for protein synthesis and cell proliferation. Ribosome subunits are assembled in the nucleolus following transcription of a 47S ribosome RNA precursor by RNA polymerase I and rRNA processing to produce mature 18S, 28S and 5.8S rRNAs. The 18S rRNA is incorporated into the ribosomal small subunit, whereas the 28S and 5.8S rRNAs are incorporated into the ribosomal large subunit. Pol I transcription and rRNA processing are coordinated processes and this coordination has been demonstrated to be mediated by a subset of U3 proteins known as t-UTPs. Up to date, five t-UTPs have been identified in humans but the mechanism(s) that function in the t-UTP(s) activation of Pol I remain unknown. In this study we have identified 1A6/DRIM, which was identified as UTP20 in our previous study, as a t-UTP. In the present study, we investigated the function and mechanism of 1A6/DRIM in Pol I transcription. Knockdown of 1A6/DRIM by siRNA resulted in a decreased 47S pre-rRNA level as determined by Northern blotting. Ectopic expression of 1A6/DRIM activated and knockdown of 1A6/DRIM inhibited the human rDNA promoter as evaluated with luciferase reporter. Chromatin immunoprecipitation (ChIP) experiments showed that 1A6/DRIM bound UBF and the rDNA promoter. Re-ChIP assay showed that 1A6/DRIM interacts with UBF at the rDNA promoter. Immunoprecipitation confirmed the interaction between 1A6/DRIM and the nucleolar acetyl-transferase hALP. It is of note that knockdown of 1A6/DRIM dramatically inhibited UBF acetylation. A finding of significance was that 1A6/DRIM depletion, as a kind of nucleolar stress, caused an increase in p53 level and inhibited cell proliferation by arresting cells at G1. We identify 1A6/DRIM as a novel t-UTP. Our results suggest that 1A6/DRIM activates Pol I transcription most likely by associating with both hALP and UBF and thereby affecting the acetylation of UBF.
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影响因子：
14.9
作者：
Meraner J;Lechner M;Loidl A;Goralik-Schramel M;Voit R;Grummt I;Loidl P
通讯作者：
Loidl P
影响因子：
16
作者：
Lapik, YR;Fernandes, CJ;Pestov, DG
通讯作者：
Pestov, DG
影响因子：
16
作者：
Grandi, P;Rybin, V;Hurt, E
通讯作者：
Hurt, E
影响因子：
10.5
作者：
JANTZEN, HM;CHOW, AM;TJIAN, R
通讯作者：
TJIAN, R
影响因子：
64.8
作者：
Dragon, F;Gallagher, JEG;Baserga, SJ
通讯作者：
Baserga, SJ