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Molecular and Cellular Biology, August 2007, p. 5365-5380, Vol. 27, No. 15
0270-7306/07/$08.00+0     doi:10.1128/MCB.00113-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

The RNA-Binding Protein HuR Promotes Cell Migration and Cell Invasion by Stabilizing the ß-actin mRNA in a U-Rich-Element-Dependent Manner{triangledown} ,{dagger}

Virginie Dormoy-Raclet,1,{ddagger} Isabelle Ménard,1,{ddagger} Eveline Clair,1 Ghada Kurban,2 Rachid Mazroui,1 Sergio Di Marco,1 Christopher von Roretz,1 Arnim Pause,2 and Imed-Eddine Gallouzi1*

Department of Biochemistry, McGill University, Quebec, Canada,1 McGill Cancer Center, McGill University, Quebec, Canada2

Received 18 January 2007/ Returned for modification 27 February 2007/ Accepted 21 May 2007

A high expression level of the ß-actin protein is required for important biological mechanisms, such as maintaining cell shape, growth, and motility. Although the elevated cellular level of the ß-actin protein is directly linked to the long half-life of its mRNA, the molecular mechanisms responsible for this effect are unknown. Here we show that the RNA-binding protein HuR stabilizes the ß-actin mRNA by associating with a uridine-rich element within its 3' untranslated region. Using RNA interference to knock down the expression of HuR in HeLa cells, we demonstrate that HuR plays an important role in the stabilization but not in the nuclear/cytoplasmic distribution of the ß-actin mRNA. HuR depletion in HeLa cells alters key ß-actin-based cytoskeleton functions, such as cell adhesion, migration, and invasion, and these defects correlate with a loss of the actin stress fiber network. Together our data establish that the posttranscriptional event involving HuR-mediated ß-actin mRNA stabilization could be a part of the regulatory mechanisms responsible for maintaining cell integrity, which is a prerequisite for avoiding transformation and tumor formation.

* Corresponding author. Mailing address: Department of Biochemistry, McGill University, McIntyre Building, Room 904, 3655 Promenade Sir William Osler, Montreal, Quebec, Canada H3G 1Y6. Phone: (514) 398-4537. Fax: (514) 398-7384. E-mail: imed.gallouzi{at}mcgill.ca

{triangledown} Published ahead of print on 4 June 2007.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

{ddagger} These two authors contributed equally to this work.

Molecular and Cellular Biology, August 2007, p. 5365-5380, Vol. 27, No. 15
0270-7306/07/$08.00+0     doi:10.1128/MCB.00113-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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