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An eIF4AIII-containing complex required for mRNA localization and nonsense-mediated mRNA decay

Nature volume 427, pages 753–757 (2004)Cite this article

Abstract

The specification of both the germ line and abdomen in Drosophila depends on the localization of oskar messenger RNA to the posterior of the oocyte1,2. This localization requires several trans-acting factors, including Barentsz and the Mago–Y14 heterodimer, which assemble with oskar mRNA into ribonucleoprotein particles (RNPs) and localize with it at the posterior pole3,4,5,6,7. Although Barentsz localization in the germ line depends on Mago–Y14, no direct interaction between these proteins has been detected5. Here, we demonstrate that the translation initiation factor eIF4AIII interacts with Barentsz and is a component of the oskar messenger RNP localization complex. Moreover, eIF4AIII interacts with Mago–Y14 and thus provides a molecular link between Barentsz and the heterodimer. The mammalian Mago (also known as Magoh)–Y14 heterodimer is a component of the exon junction complex8,9,10,11. The exon junction complex is deposited on spliced mRNAs and functions in nonsense-mediated mRNA decay (NMD)9,11,12,13,14, a surveillance mechanism that degrades mRNAs with premature translation-termination codons. We show that both Barentsz and eIF4AIII are essential for NMD in human cells. Thus, we have identified eIF4AIII and Barentsz as components of a conserved protein complex that is essential for mRNA localization in flies and NMD in mammals.

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Figure 1: Identification of eIF4AIII as a partner of Btz and Mago–Y14.
Figure 2: eIF4AIII functions with Btz in the localization of oskar mRNA.
Figure 3: eIF4AIII localizes to the nucleus and to the posterior pole of the oocyte.
Figure 4: Human eIF4AIII and Btz are required for NMD.

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Acknowledgements

We acknowledge G. Dreyfuss, A. Ephrussi, M. Moore and N. Sonenberg for sharing unpublished observations. We thank D. Micklem for the gift of GFP–Mago flies; M. Hentze, A. Kulozik and M. Kiebler for plasmids and antibodies; R. Cantera for help in collecting confocal images; and P. Lawrence for critical reading of the manuscript. I.M.P. was supported by the Royal Society Dorothy Hodgkin Fellowship. D.S.J. was supported by a Wellcome Trust Principal Research Fellowship. D.G. and E.I. are supported by the European Molecular Biology Organization.

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Authors and Affiliations

  1. Wellcome Trust/Cancer Research UK Institute and Department of Genetics, University of Cambridge, Tennis Court Road, CB2 1QR, Cambridge, UK

    Isabel M. Palacios & Daniel St Johnston

  2. EMBL, Meyerhofstrasse 1, D-69117, Heidelberg, Germany

    David Gatfield & Elisa Izaurralde

Authors
  1. Isabel M. Palacios
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  2. David Gatfield
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  4. Elisa Izaurralde
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Correspondence to Daniel St Johnston or Elisa Izaurralde.

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The authors declare that they have no competing financial interests.

Supplementary information

Supplementary Figure 1

Sequence of the conserved motifs of the DEAD-box protein family in Drosophila eIF4AIII and schematic representation of the eIF4AIII (CG7483) genomic region. (PDF 337 kb)

Supplementary Figure 2

Localisation of Staufen protein in btz1 mutant ovaries with or without a copy of the eIF4AIII19 allele. (PDF 921 kb)

Supplementary Figure 3

Conservation of the subcellular localisation of Mago:Y14, eIF4AIII and Barentsz in Drosophila egg chambers and in human HeLa cells. (PDF 814 kb)

Supplementary Figure 4

Specificity and efficiency of the siRNAs in HeLa cells. (PDF 402 kb)

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Palacios, I., Gatfield, D., St Johnston, D. et al. An eIF4AIII-containing complex required for mRNA localization and nonsense-mediated mRNA decay. Nature 427, 753–757 (2004). https://doi.org/10.1038/nature02351

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