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Nucleolin links to arsenic-induced stabilization of GADD45 mRNA

2006; Oxford University Press; Volume: 34; Issue: 2 Linguagem: Inglês

10.1093/nar/gkj459

1362-4962

Yadong Zhang, Deepak Bhatia, Hongfeng Xia, Vince Castranova, Xianglin Shi, Fei Chen,

RNA Interference and Gene Delivery

The present study shows that arsenic induces GADD45α (growth arrest and DNA damage inducible gene 45α) mainly through post-transcriptional mechanism. Treatment of the human bronchial epithelial cell line, BEAS-2B, with arsenic(III) chloride (As 3+ ) resulted in a significant increase in GADD45α protein and mRNA. However, As 3+ only exhibited a marginal effect on the transcription of the GADD45α gene. The accumulation of GADD45α mRNA is largely achieved by the stabilization of GADD45α mRNA in the cellular response to As 3+ . As 3+ is able to induce binding of mRNA stabilizing proteins, nucleolin and less potently, HuR, to the GADD45α mRNA. Although As 3+ was unable to affect the expression of nucleolin, treatment of the cells with As 3+ resulted in re-distribution of nucleolin from nucleoli to nucleoplasm. Silencing of the nucleolin mRNA by RNA interference reversed As 3+ -induced stabilization of the GADD45α mRNA and accumulation of the GADD45α protein. Stabilization of GADD45α mRNA, thus, represents a novel mechanism contributing to the production of GADD45α and cell cycle arrest in response to As 3+ .