IR@PKUHSC  > 北京大学临床肿瘤学院
学科主题临床医学
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
刊名PLOS ONE
2010-12-07
DOI10.1371/journal.pone.0014244
5期:12
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Multidisciplinary Sciences
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
英文摘要

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.

语种英语
WOS记录号WOS:000285041800004
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)
引用统计
被引频次:10[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/53275
专题北京大学临床肿瘤学院
北京大学基础医学院
北京大学临床肿瘤学院_遗传学研究室
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
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GB/T 7714
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).
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