IR@PKUHSC  > 北京大学基础医学院  > 北京大学衰老研究中心
学科主题基础医学
HuR Uses AUF1 as a Cofactor To Promote p16(INK4) mRNA Decay
Chang, Na1; Yi, Jie1; Guo, Gaier2; Liu, Xinwen1; Shang, Yongfeng1; Tong, Tanjun1; Cui, Qinghua3; Zhan, Ming4; Gorospe, Myriam5; Wang, Wengong1
刊名MOLECULAR AND CELLULAR BIOLOGY
2010-08-01
DOI10.1128/MCB.00169-10
30期:15页:3875-3886
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Biochemistry & Molecular Biology ; Cell Biology
资助者Major State Basic Research Development Program of China ; National Science Foundation of China ; Ministry of Education of the People&prime ; s Republic of China ; National Institute on Aging-IRP, National Institutes of Health ; Major State Basic Research Development Program of China ; National Science Foundation of China ; Ministry of Education of the People&prime ; s Republic of China ; National Institute on Aging-IRP, National Institutes of Health
研究领域[WOS]Biochemistry & Molecular Biology ; Cell Biology
关键词[WOS]BINDING PROTEIN HUR ; ENDOTHELIAL GROWTH-FACTOR ; ELAV-LIKE PROTEIN ; 3&prime ; -UNTRANSLATED REGION ; REPLICATIVE SENESCENCE ; STABILITY FACTOR ; TRANSLATION ; EXPRESSION ; STABILIZATION ; ELEMENT
英文摘要

In this study, we show that HuR destabilizes p16(INK4) mRNA. Although the knockdown of HuR or AUF1 increased p16 expression, concomitant AUF1 and HuR knockdown had a much weaker effect. The knockdown of Ago2, a component of the RNA-induced silencing complex (RISC), stabilized p16 mRNA. The knockdown of HuR diminished the association of the p16 3′ untranslated region (3′UTR) with AUF1 and vice versa. While the knockdown of HuR or AUF1 reduced the association of Ago2 with the p16 3′UTR, Ago2 knockdown had no influence on HuR or AUF1 binding to the p16 3′UTR. The use of EGFP-p16 chimeric reporter transcripts revealed that p16 mRNA decay depended on a stem-loop structure present in the p16 3′UTR, as HuR and AUF1 destabilized EGFP-derived chimeric transcripts bearing wild-type sequences but not transcripts with mutations in the stem-loop structure. In senescent and HuR-silenced IDH4 human diploid fibroblasts, the EGFP-p16 3′UTR transcript was more stable. Our results suggest that HuR destabilizes p16 mRNA by recruiting the RISC, an effect that depends on the secondary structure of the p16 3′UTR and requires AUF1 as a cofactor.

语种英语
所属项目编号2007CB507400 ; 30672202 ; 30621002 ; 30921062 ; 30973147 ; B07001
资助者Major State Basic Research Development Program of China ; National Science Foundation of China ; Ministry of Education of the People&prime ; s Republic of China ; National Institute on Aging-IRP, National Institutes of Health ; Major State Basic Research Development Program of China ; National Science Foundation of China ; Ministry of Education of the People&prime ; s Republic of China ; National Institute on Aging-IRP, National Institutes of Health
WOS记录号WOS:000279714500014
Citation statistics
Cited Times:66[WOS]   [WOS Record]     [Related Records in WOS]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/59561
Collection北京大学基础医学院_北京大学衰老研究中心
作者单位1.Changzhi Med Coll, Dept Biochem, Changzhi 046000, Shanxi, Peoples R China
2.Peking Univ, Res Ctr Aging, Dept Biochem & Mol Biol, Hlth Sci Ctr, Beijing 100191, Peoples R China
3.Peking Univ, Hlth Sci Ctr, Dept Med Bioinformat, Beijing 100191, Peoples R China
4.NIA, Bioinformat Unit, NIH, Baltimore, MD 21224 USA
5.NIA, Cellular & Mol Biol Lab, NIH, Baltimore, MD 21224 USA
Recommended Citation
GB/T 7714
Chang, Na,Yi, Jie,Guo, Gaier,et al. HuR Uses AUF1 as a Cofactor To Promote p16(INK4) mRNA Decay[J]. MOLECULAR AND CELLULAR BIOLOGY,2010,30(15):3875-3886.
APA Chang, Na.,Yi, Jie.,Guo, Gaier.,Liu, Xinwen.,Shang, Yongfeng.,...&Wang, Wengong.(2010).HuR Uses AUF1 as a Cofactor To Promote p16(INK4) mRNA Decay.MOLECULAR AND CELLULAR BIOLOGY,30(15),3875-3886.
MLA Chang, Na,et al."HuR Uses AUF1 as a Cofactor To Promote p16(INK4) mRNA Decay".MOLECULAR AND CELLULAR BIOLOGY 30.15(2010):3875-3886.
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