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Molecular and Cellular Biology, September 2001, p. 5889-5898, Vol. 21, No. 17
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.17.5889-5898.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Loss of HuR Is Linked to Reduced Expression of Proliferative Genes during Replicative Senescence

Wengong Wang,1 Xiaoling Yang,1 Vincent J. Cristofalo,2 Nikki J. Holbrook,1 and Myriam Gorospe1,*

Laboratory of Cellular and Molecular Biology, National Institute on Aging-Intramural Research Program, National Institutes of Health, Baltimore, Maryland 21224,1 and Lankenau Institute for Medical Research and Thomas Jefferson University, Wynnewood, Pennsylvania 190962

Received 1 May 2001/Accepted 25 May 2001

Cellular aging is accompanied by alterations in gene expression patterns. Here, using two models of replicative senescence, we describe the influence of the RNA-binding protein HuR in regulating the expression of several genes whose expression decreases during senescence. We demonstrate that HuR levels, HuR binding to target mRNAs encoding proliferative genes, and the half-lives of such mRNAs are lower in senescent cells. Importantly, overexpression of HuR in senescent cells restored a "younger" phenotype, while a reduction in HuR expression accentuated the senescent phenotype. Our studies highlight a critical role for HuR during the process of replicative senescence.

* Corresponding author. Mailing address: Box 12, Laboratory of Cellular and Molecular Biology, GRC, National Institute on Aging-IRP, NIH, 5600 Nathan Shock Dr., Baltimore, MD 21224. Phone: (410) 558-8443. Fax: (410) 558-8386. E-mail: myriam-gorospe{at}nih.gov.

Molecular and Cellular Biology, September 2001, p. 5889-5898, Vol. 21, No. 17
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.17.5889-5898.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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