UPF1 association with the cap-binding protein, CBP80, promotes nonsense-mediated mRNA decay at two distinct steps.
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.
Hwang
Jungwook
J
Department of Biochemistry and Biophysics, School of Medicine and Dentistry, University of Rochester, Rochester, NY 14642, USA.
Sato
Hanae
H
Tang
Yalan
Y
Matsuda
Daiki
D
Maquat
Lynne E
LE
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*
D018389:Codon, Nonsense; D039502:Nuclear Cap-Binding Protein Complex; D012333:RNA, Messenger; D015534:Trans-Activators; D020365:RNA Helicases; C101828:UPF1 protein, human