CBP80 promotes interaction of Upf1 with Upf2 during nonsense-mediated mRNA decay in mammalian cells

Nao Hosoda, Ki Kim Yoon, Fabrice Lejeune, Lynne E. Maquat

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120 Citations (Scopus)


In mammalian cells, nonsense-mediated messenger RNA decay (NMD) targets newly synthesized nonsense-containing mRNA bound by the cap-binding-protein heterodimer CBP80-CBP20 and at least one exon-junction complex (EJC). An EJC includes the NMD factors Upf3 or Upf3X and Upf2, and Upf2 recruits Upf1. Once this pioneer translation initiation complex is remodeled so that CBP80-CBP20 is replaced by eukaryotic initiation factor 4E, the mRNA is no longer detectably targeted for NMD. Here, we provide evidence that CBP80 augments the efficiency of NMD but not of Staufen1 (Stau1)-mediated mRNA decay (SMD). SMD depends on the recruitment of Upf1 by the RNA-binding protein Stau1 but does not depend on the other Upf proteins. We find that CBP80 interacts with Upf1 and promotes the interaction of Upf1 with Upf2 but not with Stau1.

Original languageEnglish
Pages (from-to)893-901
Number of pages9
JournalNature Structural and Molecular Biology
Issue number10
Publication statusPublished - 2005 Oct

Bibliographical note

Funding Information:
We thank E. Wolcott for technical assistance; members of the Maquat lab, especially H. Kuzmiak, for comments on the manuscript; E. Izaurralde (European Molecular Biology Laboratory, Heidelberg, Germany) for anti-CBP80; L. DesGroseillers (Université de Montreal, Montreal) for anti-Stau1; H. Baumann and B. Held (Roswell Park Cancer Institute, Buffalo, New York, USA) for anti-MUP; J. Lykke-Andersen (University of Colorado, Boulder, Colorado, USA) for anti-Upf1 and pcNMS2-UPF plasmids; N. Sonenberg (McGill Cancer Center, Montreal) for pACTAG2-HA3, pACTAG2-HA3-4E-BP1, pACTAG2-heIF4E and anti-4E-BP1; S. Morley (University of Sussex, Falmer, Brighton, UK) for pBS-Hs-CBP80 and pRSET-Hs-CBP80; J. Lewis (Anadys Pharmaceuticals, Inc., UK) for pRSET-Hs-CBP20; and F. LeRoy and S. Peltz (University of Medicine and Dentistry of New Jersey, Pistcataway, New Jersey, USA) for the FLAG-Upf1 baculovirus expression vector. This work was supported by US National Institutes of Health grant GM059614 to L.E.M.

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology


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