The eukaryotic translation initiation factor eIF4E is a critical modulator of cellular growth with functions in the nucleus and cytoplasm. In the cytoplasm, recognition of the 5′ m7G cap moiety on all mRNAs is sufficient for their functional interaction with eIF4E. In contrast, we have shown that in the nucleus eIF4E associates and promotes the nuclear export of cyclin D1, but not GAPDH or actin mRNAs. We determined that the basis of this discriminatory interaction is an ∼100-nt sequence in the 3′ untranslated region (UTR) of cyclin D1 mRNA, we refer to as an eIF4E sensitivity element (4E-SE). We found that cyclin D1 mRNA is enriched at eIF4E nuclear bodies, suggesting these are functional sites for organization of specific ribonucleoproteins. The 4E-SE is required for eIF4E to efficiently transform cells, thereby linking recognition of this element to eIF4E mediated oncogenic transformation. Our studies demonstrate previously uncharacterized fundamental differences in eIF4E-mRNA recognition between the nuclear and cytoplasmic compartments and further a novel level of regulation of cellular proliferation.
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25 April 2005
Article|
April 18 2005
eIF4E promotes nuclear export of cyclin D1 mRNAs via an element in the 3′UTR
Biljana Culjkovic,
Biljana Culjkovic
1Institute for Research in Immunology and Cancer, University of Montreal, Quebec, H3T 1J4 Canada
2Department of Physiology and Biophysics, Mount Sinai School of Medicine, New York, NY 10029
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Ivan Topisirovic,
Ivan Topisirovic
1Institute for Research in Immunology and Cancer, University of Montreal, Quebec, H3T 1J4 Canada
2Department of Physiology and Biophysics, Mount Sinai School of Medicine, New York, NY 10029
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Lucy Skrabanek,
Lucy Skrabanek
3Institute for Computational Biomedicine, Weill Medical College of Cornell University, New York, NY 10021
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Melisa Ruiz-Gutierrez,
Melisa Ruiz-Gutierrez
1Institute for Research in Immunology and Cancer, University of Montreal, Quebec, H3T 1J4 Canada
2Department of Physiology and Biophysics, Mount Sinai School of Medicine, New York, NY 10029
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Katherine L.B. Borden
Katherine L.B. Borden
1Institute for Research in Immunology and Cancer, University of Montreal, Quebec, H3T 1J4 Canada
2Department of Physiology and Biophysics, Mount Sinai School of Medicine, New York, NY 10029
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Biljana Culjkovic
1Institute for Research in Immunology and Cancer, University of Montreal, Quebec, H3T 1J4 Canada
2Department of Physiology and Biophysics, Mount Sinai School of Medicine, New York, NY 10029
Ivan Topisirovic
1Institute for Research in Immunology and Cancer, University of Montreal, Quebec, H3T 1J4 Canada
2Department of Physiology and Biophysics, Mount Sinai School of Medicine, New York, NY 10029
Lucy Skrabanek
3Institute for Computational Biomedicine, Weill Medical College of Cornell University, New York, NY 10021
Melisa Ruiz-Gutierrez
1Institute for Research in Immunology and Cancer, University of Montreal, Quebec, H3T 1J4 Canada
2Department of Physiology and Biophysics, Mount Sinai School of Medicine, New York, NY 10029
Katherine L.B. Borden
1Institute for Research in Immunology and Cancer, University of Montreal, Quebec, H3T 1J4 Canada
2Department of Physiology and Biophysics, Mount Sinai School of Medicine, New York, NY 10029
Correspondence to Katherine L.B. Borden: [email protected]
B. Culjkovic and I. Topisirovic contributed equally to this work.
Abbreviations used in this paper: CBC, cap-binding complex; ODC, ornithine decarboxylase; SNAAP, specific nucleic acids associated with protein; UTR, untranslated region.
Received:
January 06 2005
Accepted:
March 02 2005
Online ISSN: 1540-8140
Print ISSN: 0021-9525
The Rockefeller University Press
2005
J Cell Biol (2005) 169 (2): 245–256.
Article history
Received:
January 06 2005
Accepted:
March 02 2005
Citation
Biljana Culjkovic, Ivan Topisirovic, Lucy Skrabanek, Melisa Ruiz-Gutierrez, Katherine L.B. Borden; eIF4E promotes nuclear export of cyclin D1 mRNAs via an element in the 3′UTR . J Cell Biol 25 April 2005; 169 (2): 245–256. doi: https://doi.org/10.1083/jcb.200501019
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