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Published 12 September 2005. doi:10.1083/jcb.200504039
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 170, Number 6, 913-924
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Article

A role for the eIF4E-binding protein 4E-T in P-body formation and mRNA decay

Maria A. Ferraiuolo1, Sanjukta Basak1, Josee Dostie1, Elizabeth L. Murray2, Daniel R. Schoenberg2, and Nahum Sonenberg1

1 Department of Biochemistry, McGill University, Montréal, Québec H3G 1Y6, Canada
2 Department of Molecular and Cellular Biochemistry, The Ohio State University, Columbus, OH 43210

Correspondence to Nahum Sonenberg: nahum.sonenberg{at}mcgill.ca

4E-transporter (4E-T) is one of several proteins that bind the mRNA 5'cap-binding protein, eukaryotic initiation factor 4E (eIF4E), through a conserved binding motif. We previously showed that 4E-T is a nucleocytoplasmic shuttling protein, which mediates the import of eIF4E into the nucleus. At steady state, 4E-T is predominantly cytoplasmic and is concentrated in bodies that conspicuously resemble the recently described processing bodies (P-bodies), which are believed to be sites of mRNA decay. In this paper, we demonstrate that 4E-T colocalizes with mRNA decapping factors in bona fide P-bodies. Moreover, 4E-T controls mRNA half-life, because its depletion from cells using short interfering RNA increases mRNA stability. The 4E-T binding partner, eIF4E, also is localized in P-bodies. 4E-T interaction with eIF4E represses translation, which is believed to be a prerequisite for targeting of mRNAs to P-bodies. Collectively, these data suggest that 4E-T interaction with eIF4E is a priming event in inducing messenger ribonucleoprotein rearrangement and transition from translation to decay.

J. Dostie's present address is Department of Biochemistry and Molecular Pharmacology and Program in Gene Function and Expression, University of Massachusetts Medical School, Worcester, MA 01605.

Abbreviations used in this paper: 4E-T, 4E-transporter; ARE, adenine/uridine rich element; CAT, chloramphenicol acetyl transferase; eIF4E, eukaryotic initiation factor 4E; LMB, leptomycin B; LUC, luciferase; mRNP, messenger RNP; PABP, polyA binding protein; P-body, processing body; RNAi, RNA interference; siRNA, short interfering RNA; SPA, synthetic polyadenylation element.


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