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Increased stability of the p16 mRNA with replicative senescence.

ABSTRACT: Expression of p16(INK4a) is elevated during ageing and replicative senescence. Here, we report the presence of an instability determinant within the 3'-untranslated region (UTR) of the p16 messenger RNA in WI-38 human diploid fibroblasts. The p16 3'UTR was found to be a specific target of AUF1, an RNA-binding protein implicated in promoting mRNA decay. Both AUF1 levels and AUF1-p16 mRNA associations were strikingly more abundant in early-passage than late-passage fibroblast cultures. Moreover, short interfering RNA-based reductions in AUF1 levels increased the stability of p16 3'UTR-containing transcripts, elevated the expression of p16 and accentuated the senescence phenotype. Together, our findings show that p16 mRNA turnover decreases during replicative senescence and that the instability-conferring region is located within the 3'UTR of p16, as well as identifying AUF1 as a critical mediator of these regulatory events.

SUBMITTER: Wang W

PROVIDER: S-EPMC1299256 | biostudies-literature | 2005 Feb

REPOSITORIES: biostudies-literature

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Increased stability of the p16 mRNA with replicative senescence.

Wang Wengong W Martindale Jennifer L JL Yang Xiaoling X Chrest Francis J FJ Gorospe Myriam M

EMBO reports 20050201 2

Expression of p16(INK4a) is elevated during ageing and replicative senescence. Here, we report the presence of an instability determinant within the 3'-untranslated region (UTR) of the p16 messenger RNA in WI-38 human diploid fibroblasts. The p16 3'UTR was found to be a specific target of AUF1, an RNA-binding protein implicated in promoting mRNA decay. Both AUF1 levels and AUF1-p16 mRNA associations were strikingly more abundant in early-passage than late-passage fibroblast cultures. Moreover, s ...[more]

PMID: 15678155

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