Antiapoptotic function of RNA-binding protein HuR effected through prothymosin α

被引:145
作者
Lal, A [1 ]
Kawai, T [1 ]
Yang, XL [1 ]
Mazan-Mamczarz, K [1 ]
Gorospe, M [1 ]
机构
[1] NIA, LCMB, IRP, NIH, Baltimore, MD 21224 USA
关键词
ELAV; post-transcriptional gene expression; ProT alpha; stress response; translational regulation;
D O I
10.1038/sj.emboj.7600661
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We report the antiapoptotic effect of RNA-binding protein HuR, a critical regulator of the post-transcriptional fate of target transcripts. Among the most prominent mRNAs complexing with HuR is that encoding prothymosin a (ProT alpha), an inhibitor of the apoptosome. In HeLa cells, treatment with the apoptotic stimulus ultraviolet light (UVC) triggered the mobilization of ProT alpha mRNA to the cytoplasm and onto heavier polysomes, where its association with HuR increased dramatically. Analysis of a chimeric ProT alpha mRNA directly implicated HuR in regulating ProT alpha production: ProT alpha translation and cytoplasmic concentration increased in HuR-overexpressing cells and declined in cells in which HuR levels were lowered by RNA interference. Importantly, the antiapoptotic influence engendered by HuR was vitally dependent on ProT alpha expression, since use of oligomers that blocked ProT alpha translation abrogated the protective effect of HuR. Together, our data support a regulatory scheme whereby HuR binds the ProT alpha mRNA, elevates its cytoplasmic abundance and translation, and thereby elicits an antiapoptotic program.
引用
收藏
页码:1852 / 1862
页数:11
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