title: Loss of HuR is linked to reduced expression of proliferative genes during replicative senescence.
abstract: 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.
authors.affiliation: Laboratory of Cellular and Molecular Biology, National Institute on Aging-Intramural Research Program, National Institutes of Health, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA.
authors.forename: W
authors.initials: W
authors.lastname: Wang
authors.forename: X
authors.initials: X
authors.lastname: Yang
authors.forename: V J
authors.initials: VJ
authors.lastname: Cristofalo
authors.forename: N J
authors.initials: NJ
authors.lastname: Holbrook
authors.forename: M
authors.initials: M
authors.lastname: Gorospe
mesh_terms: D000368:Aged; D000375:Aging / Q000235:genetics* / Q000378:metabolism; D000954:Antigens, Surface; D002460:Cell Line; D016922:Cellular Senescence; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D010641:Phenotype; D012333:RNA, Messenger; D016601:RNA-Binding Proteins / Q000378:metabolism*; D012867:Skin / Q000166:cytology
chemical_list: D000954:Antigens, Surface; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins