|1A6/DRIM, a Novel t-UTP, Activates RNA Polymerase I Transcription and Promotes Cell Proliferation|
|Peng, Qunhui1,3; Wu, Jianguo1,3; Zhang, Ying2,3; Liu, Yun2,3; Kong, Ruirui1,3; Hu, Lelin2,3; Du, Xiaojuan2,3; Ke, Yang1,3|
|WOS标题词||Science & Technology|
|研究领域[WOS]||Science & Technology - Other Topics|
|关键词[WOS]||PRE-RIBOSOMAL-RNA ; TATA-BINDING PROTEIN ; FACTOR UBF ; RDNA TRANSCRIPTION ; GENE-EXPRESSION ; PHOSPHORYLATION ; COMPLEX ; P53 ; ACETYLATION ; RECRUITMENT|
Background: 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.
Methodology/Principal Findings: 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.
Conclusions: 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.
|项目编号||2008AA02Z131 ; 2006AA02A402 ; 30771224 ; 985-2-016-24 ; 2010CB529303|
|资助机构||National Ministry of Science and Technology ; National Natural Science Foundation of China ; Ministry of Education ; National Basic Research Program of China (973 program)|
|作者单位||1.Peking Univ, Sch Oncol, Beijing Canc Hosp & Inst, Key Lab Carcinogenesis & Translat Res Minist Educ, Beijing 100871, Peoples R China|
2.Peking Univ, Hlth Sci Ctr, Dept Cell Biol, Beijing 100871, Peoples R China
3.Peking Univ, Hlth Sci Ctr, Canc Res Ctr, Beijing 100871, Peoples R China
|Peng, Qunhui,Wu, Jianguo,Zhang, Ying,et al. 1A6/DRIM, a Novel t-UTP, Activates RNA Polymerase I Transcription and Promotes Cell Proliferation[J]. PLOS ONE,2010,5(12).|
|APA||Peng, Qunhui.,Wu, Jianguo.,Zhang, Ying.,Liu, Yun.,Kong, Ruirui.,...&Ke, Yang.(2010).1A6/DRIM, a Novel t-UTP, Activates RNA Polymerase I Transcription and Promotes Cell Proliferation.PLOS ONE,5(12).|
|MLA||Peng, Qunhui,et al."1A6/DRIM, a Novel t-UTP, Activates RNA Polymerase I Transcription and Promotes Cell Proliferation".PLOS ONE 5.12(2010).|
|1A6_DRIM, a Novel t-（719KB）||期刊论文||出版稿||开放获取||CC BY-NC-SA||浏览 请求全文|