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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Ephrussi, A., Dickinson, L. K. & Lehmann, R. Oskar organizes the germ plasm and directs localisation of the posterior determinant nanos. Cell 66, 37–50 (1991)
Kim-Ha, J., Smith, J. L. & Macdonald, P. M. oskar mRNA is localized to the posterior pole of the Drosophila oocyte. Cell 66, 23–35 (1991)
Micklem, D. R. et al. The mago nashi gene is required for the polarisation of the oocyte and the formation of perpendicular axes in Drosophila. Curr. Biol. 7, 468–478 (1997)
Newmark, P. A., Mohr, S. E., Gong, L. & Boswell, R. E. mago nashi mediates the posterior follicle cell-to-oocyte signal to organize axis formation in Drosophila. Development 124, 3197–3207 (1997)
van Eeden, F. J., Palacios, I. M., Petronczki, M., Weston, M. J. & St Johnston, D. Barentsz is essential for the posterior localisation of oskar mRNA and colocalizes with it to the posterior pole. J. Cell Biol. 154, 511–523 (2001)
Mohr, S. E., Dillon, S. T. & Boswell, R. E. The RNA-binding protein Tsunagi interacts with Mago Nashi to establish polarity and localize oskar mRNA during Drosophila oogenesis. Genes Dev. 15, 2886–2899 (2001)
Hachet, O. & Ephrussi, A. Drosophila Y14 shuttles to the posterior of the oocyte and is required for oskar mRNA transport. Curr. Biol. 11, 1666–1674 (2001)
Le Hir, H., Gatfield, D., Braun, I. C., Forler, D. & Izaurralde, E. The protein Mago provides a link between splicing and mRNA localisation. EMBO Rep. 2, 1119–1124 (2001)
Le Hir, H., Gatfield, D., Izaurralde, E. & Moore, M. J. The exon-exon junction complex provides a binding platform for factors involved in mRNA export and nonsense-mediated mRNA decay. EMBO J. 20, 4987–4997 (2001)
Kataoka, N., Diem, M. D., Kim, V. N., Yong, J. & Dreyfuss, G. Magoh, a human homolog of Drosophila Mago Nashi protein, is a component of the splicing-dependent exon-exon junction complex. EMBO J. 20, 6424–6433 (2001)
Kim, V. N. et al. The Y14 protein communicates to the cytoplasm the position of exon-exon junctions. EMBO J. 20, 2062–2068 (2001)
Gehring, N. H., Neu-Yilik, G., Schell, T., Hentze, M. W. & Kulozik, A. E. Y14 and hUpf3b form an NMD-activating complex. Mol. Cell 11, 939–949 (2003)
Fribourg, S., Gatfield, D., Izaurralde, E. & Conti, E. A novel mode of RBD-protein recognition in the Y14-Mago complex. Nature Struct. Biol. 10, 433–439 (2003)
Lykke-Andersen, J., Shu, M. D. & Steitz, J. A. Communication of the position of exon-exon junctions to the mRNA surveillance machinery by the protein RNPS1. Science 293, 1836–1839 (2001)
Grosshans, J., Schnorrer, F. & Nusslein-Volhard, C. Oligomerisation of Tube and Pelle leads to nuclear localisation of dorsal. Mech. Dev. 81, 127–138 (1999)
Weinstein, D. C., Honore, E. & Hemmati-Brivanlou, A. Epidermal induction and inhibition of neural fate by translation initiation factor 4AIII. Development 124, 4235–4242 (1997)
Li, Q. et al. Eukaryotic translation initiation factor 4AIII (eIF4AIII) is functionally distinct from eIF4AI and eIF4AII. Mol. Cell. Biol. 19, 7336–7346 (1999)
Tanner, N. K., Cordin, O., Banroques, J., Doere, M. & Linder, P. The Q motif: a newly identified motif in DEAD box helicases may regulate ATP binding and hydrolysis. Mol. Cell 11, 127–138 (2003)
Baker, B. S., Hoff, G., Kaufman, T. C., Wolfner, M. F. & Hazelrigg, T. The doublesex locus of Drosophila melanogaster and its flanking regions: a cytogenetic analysis. Genetics 127, 125–138 (1991)
St Johnston, D., Beuchle, D. & Nusslein-Volhard, C. Staufen, a gene required to localize maternal RNAs in the Drosophila egg. Cell 66, 51–63 (1991)
Smith, R. Screens to Find Novel Genes Involved in Pole Plasm Formation in Drosophila melanogaster. PhD Thesis, Cambridge Univ. (1998)
Macchi, P. et al. Barentsz, a new component of the Staufen-containing ribonucleoprotein particles in mammalian cells, interacts with Staufen in an RNA-dependent manner. J. Neurosci. 23, 5778–5788 (2003)
Thermann, R. et al. Binary specification of nonsense codons by splicing and cytoplasmic translation. EMBO J. 17, 3484–3494 (1998)
Mendell, J. T., ap Rhys, C. M. & Dietz, H. C. Separable roles for rent1/hUpf1 in altered splicing and decay of nonsense transcripts. Science 298, 419–422 (2002)
Gatfield, D., Unterholzner, L., Ciccarelli, F. D., Bork, P. & Izaurralde, E. Nonsense-mediated mRNA decay in Drosophila: at the intersection of the yeast and mammalian pathways. EMBO J. 22, 3960–3970 (2003)
Chan, C. C. et al. eIF4A3 is a novel component of the exon junction complex. RNA 10, 200–209 (2004)
Hollenberg, S. M., Sternglanz, R., Cheng, P. F. & Weintraub, H. Identification of a new family of tissue-specific basic helix-loop-helix proteins with a two-hybrid system. Mol. Cell. Biol. 15, 3813–3822 (1995)
Chou, T. B. & Perrimon, N. The autosomal FLP-DFS technique for generating germline mosaics in Drosophila melanogaster. Genetics 144, 1673–1679 (1996)
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.
The authors declare that they have no competing financial interests.
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)
Localisation of Staufen protein in btz1 mutant ovaries with or without a copy of the eIF4AIII19 allele. (PDF 921 kb)
Conservation of the subcellular localisation of Mago:Y14, eIF4AIII and Barentsz in Drosophila egg chambers and in human HeLa cells. (PDF 814 kb)
Specificity and efficiency of the siRNAs in HeLa cells. (PDF 402 kb)
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