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Nucleic Acids Research 2006 34(2):485-495; doi:10.1093/nar/gkj459
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Published online 18 January 2006

© The Author 2006. Published by Oxford University Press. All rights reserved
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions{at}oxfordjournals.org

Article

Nucleolin links to arsenic-induced stabilization of GADD45{alpha} mRNA

Yadong Zhang1,2, Deepak Bhatia3, Hongfeng Xia1, Vince Castranova3, Xianglin Shi1,3 and Fei Chen2,3,*

1Institute for Nutritional Sciences, Chinese Academy of Sciences Shanghai 200031, China 2School of Medicine, West Virginia University Morgantown, WV 26506, USA 3The Health Effects Laboratory Division, National Institute for Occupational Safety and Health Morgantown, WV 26505, USA

*To whom correspondence should be addressed at PPRB/NIOSH, Room L2015, 1095 Willowdale Road, Morgantown, WV 26505, USA. Tel: +1 304 285 6021; Fax: +1 304 285 5938; Email: lfd3{at}cdc.gov

Received November 20, 2005. Revised January 5, 2006. Accepted January 5, 2006.

The present study shows that arsenic induces GADD45{alpha} (growth arrest and DNA damage inducible gene 45{alpha}) mainly through post-transcriptional mechanism. Treatment of the human bronchial epithelial cell line, BEAS-2B, with arsenic(III) chloride (As3+) resulted in a significant increase in GADD45{alpha} protein and mRNA. However, As3+ only exhibited a marginal effect on the transcription of the GADD45{alpha} gene. The accumulation of GADD45{alpha} mRNA is largely achieved by the stabilization of GADD45{alpha} mRNA in the cellular response to As3+. As3+ is able to induce binding of mRNA stabilizing proteins, nucleolin and less potently, HuR, to the GADD45{alpha} mRNA. Although As3+ was unable to affect the expression of nucleolin, treatment of the cells with As3+ resulted in re-distribution of nucleolin from nucleoli to nucleoplasm. Silencing of the nucleolin mRNA by RNA interference reversed As3+-induced stabilization of the GADD45{alpha} mRNA and accumulation of the GADD45{alpha} protein. Stabilization of GADD45{alpha} mRNA, thus, represents a novel mechanism contributing to the production of GADD45{alpha} and cell cycle arrest in response to As3+.

The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors


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