Binding of a novel SMG-1–Upf1–eRF1–eRF3 complex (SURF) to the exon junction complex triggers Upf1 phosphorylation and nonsense-mediated mRNA decay
- Isao Kashima1,6,
- Akio Yamashita1,6,
- Natsuko Izumi1,
- Naoyuki Kataoka2,
- Ryo Morishita3,
- Shinichi Hoshino4,
- Mutsuhito Ohno2,
- Gideon Dreyfuss5, and
- Shigeo Ohno1,7
- 1Department of Molecular Biology, Yokohama City University School of Medicine, Yokohama 236-0004, Japan; 2Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan; 3CellFree Sciences, Ono-cho,Tsurumi-ku,Yokohama 230-0046, Japan; 4Preventive Nutraceutical Sciences, Nagoya City University, Nagoya 467-8603, Japan; 5Howard Hughes Medical Institute and Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
Abstract
Nonsense-mediated mRNA decay (NMD) is a surveillance mechanism that degrades mRNA containing premature termination codons (PTCs). In mammalian cells, recognition of PTCs requires translation and depends on the presence on the mRNA with the splicing-dependent exon junction complex (EJC). While it is known that a key event in the triggering of NMD is phosphorylation of the trans-acting factor, Upf1, by SMG-1, the relationship between Upf1 phosphorylation and PTC recognition remains undetermined. Here we show that SMG-1 binds to the mRNA-associated components of the EJC, Upf2, Upf3b, eIF4A3, Magoh, and Y14. Further, we describe a novel complex that contains the NMD factors SMG-1 and Upf1, and the translation termination release factors eRF1 and eRF3 (SURF). Importantly, an association between SURF and the EJC is required for SMG-1-mediated Upf1 phosphorylation and NMD. Thus, the SMG-1-mediated phosphorylation of Upf1 occurs on the association of SURF with EJC, which provides the link between the EJC and recognition of PTCs and triggers NMD.
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Footnotes
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Supplemental material is available at http://www.genesdev.org.
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Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.1389006.
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↵6 These authors contributed equally to this work.
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↵7 Corresponding author.
↵7 E-MAIL ohnos{at}med.yokohama-cu.ac.jp; FAX 81-45-785-4140.
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- Accepted December 13, 2005.
- Received October 31, 2005.
- Cold Spring Harbor Laboratory Press