Article
- The EMBO Journal (2005) 24, 1852 - 1862
- doi:10.1038/sj.emboj.7600661
Published online: 28 April 2005
Subject Categories:
Antiapoptotic function of RNA-binding protein HuR effected through prothymosin 
Ashish Lal1, Tomoko Kawai1, Xiaoling Yang1, Krystyna Mazan-Mamczarz1 and Myriam Gorospe1
- Laboratory of Cellular and Molecular Biology, National Institute on Aging-IRP, National Institutes of Health, Baltimore, MD, USA
Correspondence to:
Myriam Gorospe, Box 12, LCMB, NIA-IRP, NIH 5600 Nathan Shock Drive, Baltimore, MD 21224, USA. Tel.: +1 410 558 8443; Fax: +1 410 558 8386; E-mail: myriam-gorospe@nih.gov
Received 1 December 2004; Accepted 5 April 2005
Abstract
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 
(ProT), an inhibitor of the apoptosome. In HeLa cells, treatment with the apoptotic stimulus ultraviolet light (UVC) triggered the mobilization of ProT mRNA to the cytoplasm and onto heavier polysomes, where its association with HuR increased dramatically. Analysis of a chimeric ProT mRNA directly implicated HuR in regulating ProT production: ProT 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 expression, since use of oligomers that blocked ProT translation abrogated the protective effect of HuR. Together, our data support a regulatory scheme whereby HuR binds the ProT mRNA, elevates its cytoplasmic abundance and translation, and thereby elicits an antiapoptotic program.
Keywords:
- ELAV,
- post-transcriptional gene expression,
- ProT,
- stress response,
- translational regulation
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