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学科主题: 基础医学
题名:
Transcriptional Repressor NIR Functions in the Ribosome RNA Processing of Both 40S and 60S Subunits
作者: Wu, Jianguo1; Zhang, Ying1; Wang, Yingshuang1; Kong, Ruirui1; Hu, Lelin2; Schuele, Roland3; Du, Xiaojuan2; Ke, Yang1
刊名: PLOS ONE
发表日期: 2012-02-20
DOI: 10.1371/journal.pone.0031692
卷: 7, 期:2
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]: SMALL NUCLEOLAR RNA ; CELL-CYCLE ; U8 SNORNA ; PROTEIN-SYNTHESIS ; BINDING-PROTEIN ; POLYMERASE-I ; P53 ; BIOGENESIS ; MDM2 ; BOP1
英文摘要:

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.

语种: 英语
所属项目编号: 81071672 ; 81171877 ; 985-2-016-24 ; 2008AA02Z131 ; 2010CB529303
项目资助者: National Natural Science Foundation of China ; Key Construction Program of the National "985&prime ; &prime ; Project ; National High Technology Research and Development Program of China (863 Program) ; National Basic Research Program of China (973program)
WOS记录号: WOS:000302871500076
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/55123
Appears in Collections:基础医学院_细胞生物学系_期刊论文

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作者单位: 1.Peking Univ, Beijing Canc Hosp & Inst, Key Lab Carcinogenesis & Translat Res, Minist Educ,Genet Lab,Sch Oncol, Beijing 100871, Peoples R China
2.Peking Univ, Hlth Sci Ctr, Dept Cell Biol, Sch Basic Med Sci, Beijing 100871, Peoples R China
3.Univ Freiburg, Med Res Ctr, D-79106 Freiburg, Germany

Recommended Citation:
Wu, Jianguo,Zhang, Ying,Wang, Yingshuang,et al. Transcriptional Repressor NIR Functions in the Ribosome RNA Processing of Both 40S and 60S Subunits[J]. PLOS ONE,2012,7(2).
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