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Vol. 18, Issue 12, 5048-5059, December 2007

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Cytoplasmic Relocalization of Heterogeneous Nuclear Ribonucleoprotein A1 Controls Translation Initiation of Specific mRNAs

Anne Cammas^*,,,, Frédéric Pileur^*,,,, Sophie Bonnal^*,,,||, Stephen M. Lewis^¶, Nicolas Lévêque^#, Martin Holcik^¶, and Stéphan Vagner^*,,,

*Institut National de la Santé et de la Recherche Médicale U563, Toulouse, F-31000, France; Institut Claudius Regaud, Toulouse, F-31052, France; Université Toulouse III Paul Sabatier, Toulouse, F-31000, France; ^¶Apoptosis Research Centre, Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Ontario, K1H 8L1, Canada; and ^#Laboratoire de Virologie et Pathologie Humaine, Centre National de la Recherche Scientifique FRE 3011, Université Claude Bernard Lyon 1, Faculté de Médecine RTH Laënnec, F-69372 Lyon, France

Submitted June 25, 2007; Revised September 7, 2007; Accepted September 14, 2007
Monitoring Editor: Marvin P. Wickens

Heterogeneous nuclear ribonucleoprotein (hnRNP) A1 is a nucleocytoplasmic shuttling protein that regulates gene expression through its action on mRNA metabolism and translation. The cytoplasmic redistribution of hnRNP A1 is a regulated process during viral infection and cellular stress. Here, we show that hnRNP A1 is an internal ribosome entry site (IRES) trans-acting factor that binds specifically to the 5' untranslated region of both the human rhinovirus-2 and the human apoptotic peptidase activating factor 1 (apaf-1) mRNAs, thereby regulating their translation. Furthermore, the cytoplasmic redistribution of hnRNP A1 after rhinovirus infection leads to enhanced rhinovirus IRES-mediated translation, whereas the cytoplasmic relocalization of hnRNP A1 after UVC irradiation limits the UVC-triggered translational activation of the apaf-1 IRES. Therefore, this study provides a direct demonstration that IRESs behave as translational enhancer elements regulated by specific trans-acting mRNA binding proteins in given physiological conditions. Our data highlight a new way to regulate protein synthesis in eukaryotes through the subcellular relocalization of a nuclear mRNA-binding protein.

The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).

These authors contributed equally to this work.

^|| Present address: Parc de Recerca Biomèdica de Barcelona (PRBB), Centre de Regulació Genòmica (CRG) c/ Dr. Aiguader, 88, Planta 6, 08003 Barcelona, Spain.

Address correspondence to: Stéphan Vagner (vagner{at}toulouse.inserm.fr).