Abstract
The exon junction complex (EJC), a set of proteins deposited on mRNAs as a consequence of pre-mRNA splicing, is a key effector of downstream mRNA metabolism. We have identified eIF4AIII, a member of the eukaryotic translation initiation factor 4A family of RNA helicases (also known as DExH/D box proteins), as a novel EJC core component. Crosslinking and antibody inhibition studies suggest that eIF4AIII constitutes at least part of the platform anchoring other EJC components to spliced mRNAs. A nucleocytoplasmic shuttling protein, eIF4AIII associates in vitro and in vivo with two other EJC core factors, Y14 and Magoh. In mammalian cells, eIF4AIII is essential for nonsense-mediated mRNA decay (NMD). Finally, a model is proposed by which eIF4AIII represents a new functional class of DExH/D box proteins that act as RNA clamps or 'place holders' for the sequence-independent attachment of additional factors to RNAs.
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Acknowledgements
We thank E. Izaurralde, R. Reed and J. Steitz for plasmids and antibodies against Y14 and Magoh. We are grateful to G. Dreyfuss, E. Izaurralde and R. Reed for communicating results prior to publication. We acknowledge our laboratory members, especially M. Jurica, A. Nott, F. LaRiviere and C. Mock-Casagrande for helpful advice and discussions. We are grateful to N. Levin for synthesizing siRNA oligos. M.J.M. is a Howard Hughes Medical Institute associate investigator. This work was supported in part by US National Institutes of Health grant GM53007 (M.J.M.) and a research stipend from the Alfred Benzon Foundation (T.Ø.T.).
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Shibuya, T., Tange, T., Sonenberg, N. et al. eIF4AIII binds spliced mRNA in the exon junction complex and is essential for nonsense-mediated decay. Nat Struct Mol Biol 11, 346–351 (2004). https://doi.org/10.1038/nsmb750
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DOI: https://doi.org/10.1038/nsmb750
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