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Molecular and Cellular Biology, September 2001, p. 5889-5898, Vol. 21, No. 17
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.
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
*
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.
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