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

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 alpha (ProTalpha), an inhibitor of the apoptosome. In HeLa cells, treatment with the apoptotic stimulus ultraviolet light (UVC) triggered the mobilization of ProTalpha mRNA to the cytoplasm and onto heavier polysomes, where its association with HuR increased dramatically. Analysis of a chimeric ProTalpha mRNA directly implicated HuR in regulating ProTalpha production: ProTalpha 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 ProTalpha expression, since use of oligomers that blocked ProTalpha translation abrogated the protective effect of HuR. Together, our data support a regulatory scheme whereby HuR binds the ProTalpha mRNA, elevates its cytoplasmic abundance and translation, and thereby elicits an antiapoptotic program.