title: UPF1 association with the cap-binding protein, CBP80, promotes nonsense-mediated mRNA decay at two distinct steps.
abstract: Nonsense-mediated mRNA decay (NMD) is an mRNA surveillance mechanism that in mammals generally occurs upon recognition of a premature termination codon (PTC) during a pioneer round of translation. This round involves newly synthesized mRNA that is bound at its 5' end by the cap-binding protein (CBP) heterodimer CBP80-CBP20. Here we show that precluding the binding of the NMD factor UPF1 to CBP80 inhibits NMD at two steps: the association of SMG1 and UPF1 with the two eukaryotic release factors (eRFs) during SURF complex formation at a PTC, and the subsequent association of SMG1 and UPF1 with an exon-junction complex. We also demonstrate that UPF1 binds PTC-containing mRNA more efficiently than the corresponding PTC-free mRNA in a way that is promoted by the UPF1-CBP80 interaction. A unifying model proposes a choreographed series of protein-protein interactions occurring on an NMD target.
authors.affiliation: Department of Biochemistry and Biophysics, School of Medicine and Dentistry, University of Rochester, Rochester, NY 14642, USA.
authors.forename: Jungwook
authors.initials: J
authors.lastname: Hwang
authors.forename: Hanae
authors.initials: H
authors.lastname: Sato
authors.forename: Yalan
authors.initials: Y
authors.lastname: Tang
authors.forename: Daiki
authors.initials: D
authors.lastname: Matsuda
authors.forename: Lynne E
authors.initials: LE
authors.lastname: Maquat
mesh_terms: D018389:Codon, Nonsense; D006367:HeLa Cells; D006801:Humans; D008954:Models, Biological; D039502:Nuclear Cap-Binding Protein Complex / Q000235:genetics / Q000378:metabolism*; D020365:RNA Helicases; D020871:RNA Stability / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*
chemical_list: D018389:Codon, Nonsense; D039502:Nuclear Cap-Binding Protein Complex; D012333:RNA, Messenger; D015534:Trans-Activators; D020365:RNA Helicases; C101828:UPF1 protein, human