Loss of HuR is linked to reduced expression of proliferative genes during replicative senescence

Cellular aging is accompanied by alterations in gene expression patterns. H ere, using two models of replicative senescence, we describe the influence of the RNA-binding protein HuR in regulating the expression of several gene s whose expression decreases during senescence. We demonstrate that HuR lev els, HuR binding to target mRNAs encoding proliferative genes, and the half -lives of such mRNAs are lower in senescent cells. Importantly, overexpress ion of HuR in senescent cells restored a "younger" phenotype, while a reduc tion in HuR expression accentuated the senescent phenotype. Our studies hig hlight a critical role for HuR during the process of replicative senescence .