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Molecular and Cellular Biology, August 2006, p. 5744-5758, Vol. 26, No. 15
0270-7306/06/$08.00+0 doi:10.1128/MCB.00224-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.
hnRNP A1 Relocalization to the Stress Granules Reflects a Role in the Stress Response
Sonia Guil,
Jennifer C. Long, and
Javier F. Cáceres*
Medical Research Council Human Genetics Unit, Western General Hospital, Edinburgh, Scotland, United Kingdom
Received 7 February 2006/
Returned for modification 1 March 2006/
Accepted 9 May 2006
hnRNP A1 is a nucleocytoplasmic shuttling protein that is involved in many aspects of mRNA metabolism. We have previously shown that activation of the p38 stress-signaling pathway in mammalian cells results in both hyperphosphorylation and cytoplasmic accumulation of hnRNP A1, affecting alternative splicing regulation in vivo. Here we show that the stress-induced cytoplasmic accumulation of hnRNP A1 occurs in discrete phase-dense particles, the cytoplasmic stress granules (SGs). Interestingly, mRNA-binding activity is required for both phosphorylation of hnRNP A1 and localization to SGs. We also show that these effects are mediated by the Mnk1/2 protein kinases that act downstream of p38. Finally, depletion of hnRNP A1 affects the recovery of cells from stress, suggesting a physiologically significant role for hnRNP A1 in the stress response. Our data are consistent with a model whereby hnRNP A1 recruitment to SGs involves Mnk1/2-dependent phosphorylation of mRNA-bound hnRNP A1.
* Corresponding author. Mailing address: MRC Human Genetics Unit, Western General Hospital, Crewe Rd., Edinburgh EH4 2XU, United Kingdom. Phone: 44 131 467 8426. Fax: 44 131 467 8456. E-mail: Javier.Caceres{at}hgu.mrc.ac.uk.
Molecular and Cellular Biology, August 2006, p. 5744-5758, Vol. 26, No. 15
0270-7306/06/$08.00+0 doi:10.1128/MCB.00224-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.
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Copyright © 2006 by the American Society for Microbiology. All rights reserved.