Article abstract
Nature Structural & Molecular Biology 15, 85 - 93 (2008)
Published online: 9 December 2007 | doi:10.1038/nsmb1330
NMD factors UPF2 and UPF3 bridge UPF1 to the exon junction complex and stimulate its RNA helicase activity
Hala Chamieh1,3, Lionel Ballut1,2,3, Fabien Bonneau1 & Hervé Le Hir1
Abstract
Nonsense-mediated mRNA decay (NMD) eliminates mRNAs containing a premature translation termination codon through the recruitment of the conserved NMD factors UPF1, UPF2 and UPF3. In humans, a dynamic assembly pathway allows UPF1 to join UPF2 and UPF3 recruited to the mRNA by the exon-junction complex (EJC). Here we show that the recombinant EJC core is sufficient to reconstitute, with the three UPF proteins, a stable heptameric complex on RNA. The EJC proteins MAGOH, Y14 and eIF4AIII provide a composite binding site for UPF3b that serves as a bridge to UPF2 and UPF1. In the UPF trimeric complex, UPF2 and UPF3b cooperatively stimulate both ATPase and RNA helicase activities of UPF1. This work demonstrates that the EJC core is sufficient to stably anchor the UPF proteins to mRNA and provides insights into the regulation of its central effector, UPF1.
- Equipe Labélisée La Ligue, Centre de Génétique Moléculaire, CNRS UPR 2167, Associée aux Universités Paris 6 et Paris 11, Avenue de la terrasse, Gif-sur-Yvette, F-91198, France.
- Present addresses: IBCP, CNRS UMR5086, Université de Lyon 1, France (L.B.); Max Planck Institute of Biochemistry, Department of Structural Cell Biology, Am Klopferspitz 18, D-82152 Martinsried, Germany (F.B.).
- These authors contributed equally to this work.
Correspondence to: Hervé Le Hir1 e-mail: herve.lehir@cgm.cnrs-gif.fr
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