Binding of a Novel SMG-1-Upf1-eRF1-eRF3 Complex (SURF) to the Exon Junction Complex Triggers Upf1 Phosphorylation and Nonsense-mediated MRNA Decay

Overview

Journal Genes Dev

Specialty Molecular Biology

Date 2006 Feb 3

PMID 16452507

Citations 348

Authors

Isao Kashima

Akio Yamashita

Natsuko Izumi

Naoyuki Kataoka

Ryo Morishita

Shinichi Hoshino

Mutsuhito Ohno

Gideon Dreyfuss

Shigeo Ohno

Affiliations

Soon will be listed here.

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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References

Ohnishi T, Yamashita A, Kashima I, Schell T, Anders K, Grimson A . Phosphorylation of hUPF1 induces formation of mRNA surveillance complexes containing hSMG-5 and hSMG-7. Mol Cell. 2003; 12(5):1187-200. DOI: 10.1016/s1097-2765(03)00443-x. View

He F, Li X, Spatrick P, Casillo R, Dong S, Jacobson A . Genome-wide analysis of mRNAs regulated by the nonsense-mediated and 5' to 3' mRNA decay pathways in yeast. Mol Cell. 2003; 12(6):1439-52. DOI: 10.1016/s1097-2765(03)00446-5. View

Chan C, Dostie J, Diem M, Feng W, Mann M, Rappsilber J . eIF4A3 is a novel component of the exon junction complex. RNA. 2004; 10(2):200-9. PMC: 1370532. DOI: 10.1261/rna.5230104. View

de Pinto B, Lippolis R, Castaldo R, Altamura N . Overexpression of Upf1p compensates for mitochondrial splicing deficiency independently of its role in mRNA surveillance. Mol Microbiol. 2004; 51(4):1129-42. DOI: 10.1046/j.1365-2958.2003.03889.x. View

Palacios I, Gatfield D, St Johnston D, Izaurralde E . An eIF4AIII-containing complex required for mRNA localization and nonsense-mediated mRNA decay. Nature. 2004; 427(6976):753-7. DOI: 10.1038/nature02351. View

Moore M . From birth to death: the complex lives of eukaryotic mRNAs. Science. 2005; 309(5740):1514-8. DOI: 10.1126/science.1111443. View

Hosoda N, Kim Y, Lejeune F, Maquat L . CBP80 promotes interaction of Upf1 with Upf2 during nonsense-mediated mRNA decay in mammalian cells. Nat Struct Mol Biol. 2005; 12(10):893-901. DOI: 10.1038/nsmb995. View

Gehring N, Kunz J, Neu-Yilik G, Breit S, Viegas M, Hentze M . Exon-junction complex components specify distinct routes of nonsense-mediated mRNA decay with differential cofactor requirements. Mol Cell. 2005; 20(1):65-75. DOI: 10.1016/j.molcel.2005.08.012. View

Yamashita A, Kashima I, Ohno S . The role of SMG-1 in nonsense-mediated mRNA decay. Biochim Biophys Acta. 2005; 1754(1-2):305-15. DOI: 10.1016/j.bbapap.2005.10.002. View

10.

Fukuhara N, Ebert J, Unterholzner L, Lindner D, Izaurralde E, Conti E . SMG7 is a 14-3-3-like adaptor in the nonsense-mediated mRNA decay pathway. Mol Cell. 2005; 17(4):537-47. DOI: 10.1016/j.molcel.2005.01.010. View

11.

Mitrovich Q, Anderson P . Unproductively spliced ribosomal protein mRNAs are natural targets of mRNA surveillance in C. elegans. Genes Dev. 2000; 14(17):2173-84. PMC: 316897. DOI: 10.1101/gad.819900. View

12.

Zhou Z, Luo M, Straesser K, Katahira J, Hurt E, REED R . The protein Aly links pre-messenger-RNA splicing to nuclear export in metazoans. Nature. 2000; 407(6802):401-5. DOI: 10.1038/35030160. View

13.

Kataoka N, Yong J, Kim V, Velazquez F, Perkinson R, Wang F . Pre-mRNA splicing imprints mRNA in the nucleus with a novel RNA-binding protein that persists in the cytoplasm. Mol Cell. 2000; 6(3):673-82. DOI: 10.1016/s1097-2765(00)00065-4. View

14.

Maquat L . Nonsense-mediated mRNA decay: splicing, translation and mRNP dynamics. Nat Rev Mol Cell Biol. 2004; 5(2):89-99. DOI: 10.1038/nrm1310. View

15.

Ferraiuolo M, Lee C, Ler L, Hsu J, Costa-Mattioli M, Luo M . A nuclear translation-like factor eIF4AIII is recruited to the mRNA during splicing and functions in nonsense-mediated decay. Proc Natl Acad Sci U S A. 2004; 101(12):4118-23. PMC: 384704. DOI: 10.1073/pnas.0400933101. View

16.

Kadlec J, Izaurralde E, Cusack S . The structural basis for the interaction between nonsense-mediated mRNA decay factors UPF2 and UPF3. Nat Struct Mol Biol. 2004; 11(4):330-7. DOI: 10.1038/nsmb741. View

17.

Shibuya T, Tange T, Sonenberg N, Moore M . eIF4AIII binds spliced mRNA in the exon junction complex and is essential for nonsense-mediated decay. Nat Struct Mol Biol. 2004; 11(4):346-51. DOI: 10.1038/nsmb750. View

18.

Chiu S, Lejeune F, Ranganathan A, Maquat L . The pioneer translation initiation complex is functionally distinct from but structurally overlaps with the steady-state translation initiation complex. Genes Dev. 2004; 18(7):745-54. PMC: 387415. DOI: 10.1101/gad.1170204. View

19.

Usuki F, Yamashita A, Higuchi I, Ohnishi T, Shiraishi T, Osame M . Inhibition of nonsense-mediated mRNA decay rescues the phenotype in Ullrich's disease. Ann Neurol. 2004; 55(5):740-4. DOI: 10.1002/ana.20107. View

20.

Tange T, Nott A, Moore M . The ever-increasing complexities of the exon junction complex. Curr Opin Cell Biol. 2004; 16(3):279-84. DOI: 10.1016/j.ceb.2004.03.012. View