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学科主题: 基础医学
题名:
Reduced nuclear export of HuR mRNA by HuR is linked to the loss of HuR in replicative senescence
作者: Yi, Jie1; Chang, Na1; Liu, Xinwen1; Guo, Gaier2; Xue, Lixiang1; Tong, Tanjun1; Gorospe, Myriam3; Wang, Wengong1
刊名: NUCLEIC ACIDS RESEARCH
发表日期: 2010-03-01
DOI: 10.1093/nar/gkp1114
卷: 38, 期:5, 页:1547-1558
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biochemistry & Molecular Biology
研究领域[WOS]: Biochemistry & Molecular Biology
关键词[WOS]: BINDING PROTEIN HUR ; INCREASED CYCLOOXYGENASE-2 EXPRESSION ; ELAV-LIKE PROTEIN ; CYTOPLASMIC HUR ; CELL-PROLIFERATION ; OVARIAN-CARCINOMA ; PROGNOSTIC-FACTOR ; BREAST-CARCINOMA ; STABILITY FACTOR ; CD83 EXPRESSION
英文摘要:

The RNA-binding protein, HuR, associates with the HuR mRNA, but the consequences of this interaction are unknown. Here, we use human diploid fibroblasts (HDFs) and cervical carcinoma cells to study this regulatory paradigm. Ectopic overexpression of HuR potently enhanced the translation and cytoplasmic levels of endogenous HuR, but did not affect HuR mRNA levels. Inhibition of CRM1 function by Lemptomycin B or by knockdown of CRM1 greatly diminished the cytoplasmic levels of endogenous HuR mRNA and hence blocked the induction of endogenous HuR by exogenous HuR. Further studies showed that HuR interacted with the 3′-untranslated region (UTR) of HuR and that overexpression of HuR increased the cytoplasmic levels of a chimeric luciferase-HuR 3′-UTR reporter transcript, as well as luciferase activity; conversely, HuR knockdown reduced both parameters. Moreover, the loss of HuR in senescent, late-passage HDFs was accompanied by a reduced cytoplasmic presence of endogenous HuR mRNA, ectopic Luc-HuR-3′UTR reporter transcript, and luciferase activity relative to what was observed in young, early-passage cells. Our results reveal a positive feedback mechanism for the regulation of HuR, which may play an important role in the regulation of HuR during replicative senescence.

语种: 英语
所属项目编号: 2007CB507400 ; 30672202 ; 30621002 ; B07001
项目资助者: Major State Basic Research Development Program of China ; National Science Foundation of China ; Ministry of Education of People&prime ; s Republic of China ; National Institute on Aging-IRP, National Institutes of Health
WOS记录号: WOS:000276304500018
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/55614
Appears in Collections:基础医学院_北京大学衰老研究中心_期刊论文

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作者单位: 1.Changzhi Med Coll, Dept Biochem, Changzhi 046000, Shanxi, Peoples R China
2.Peking Univ, Hlth Sci Ctr, Res Ctr Aging, Dept Biochem & Mol Biol, Beijing 100083, Peoples R China
3.NIA, Lab Cellular & Mol Biol, NIH, Baltimore, MD 21224 USA

Recommended Citation:
Yi, Jie,Chang, Na,Liu, Xinwen,et al. Reduced nuclear export of HuR mRNA by HuR is linked to the loss of HuR in replicative senescence[J]. NUCLEIC ACIDS RESEARCH,2010,38(5):1547-1558.
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