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

作者：Lal A; Kawai T; Yang XL; Mazan Mamczarz K; Gorospe M^*

来源：The EMBO Journal, 2005, 24(10): 1852-1862.

DOI：10.1038/sj.emboj.7600661

• ELAV
• post-transcriptional gene expression
• ProT alpha
• stress response
• translational regulation

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.

• 出版日期2005-5-18