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Published online 30 October 2006. doi:10.1083/jcb.200607020
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 175, Number 3, 415-426
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Article

 eIF4E is a central node of an RNA regulon that governs cellular proliferation

Biljana Culjkovic1,2, Ivan Topisirovic1,2, Lucy Skrabanek3, Melisa Ruiz-Gutierrez1,2, and Katherine L.B. Borden1,2

1 Institute for Research in Immunology and Cancer and 2 Department of Pathology and Cell Biology, Université de Montréal, Montréal, Québec H4M 1J6, Canada
3 Institute for Computational Biomedicine, Weill Medical College of Cornell University, New York, NY 10021

Correspondence to Katherine L.B. Borden: katherine.borden{at}umontreal.ca

This study demonstrates that the eukaryotic translation initiation factor eIF4E is a critical node in an RNA regulon that impacts nearly every stage of cell cycle progression. Specifically, eIF4E coordinately promotes the messenger RNA (mRNA) export of several genes involved in the cell cycle. A common feature of these mRNAs is a structurally conserved, ~50-nucleotide element in the 3' untranslated region denoted as an eIF4E sensitivity element. This element is sufficient for localization of capped mRNAs to eIF4E nuclear bodies, formation of eIF4E-specific ribonucleoproteins in the nucleus, and eIF4E-dependent mRNA export. The roles of eIF4E in translation and mRNA export are distinct, as they rely on different mRNA elements. Furthermore, eIF4E-dependent mRNA export is independent of ongoing RNA or protein synthesis. Unlike the NXF1-mediated export of bulk mRNAs, eIF4E-dependent mRNA export is CRM1 dependent. Finally, the growth-suppressive promyelocytic leukemia protein (PML) inhibits this RNA regulon. These data provide novel perspectives into the proliferative and oncogenic properties of eIF4E.

Abbreviations used in this paper: 4E-SE, eIF4E sensitivity element; EMSA, electromobility shift assay; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; IP, immunoprecipitation; LMB, leptomycin B; ODC, ornithine decarboxylase; PML, promyelocytic leukemia protein; PRH, proline-rich homeodomain; rRNA, ribosomal RNA; SLP, stem loop pair; USER, untranslated sequence elements for regulation; UsnRNA, U small nuclear RNA; UTR, untranslated region.


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