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UPF1 Association with the Cap-Binding Protein, CBP80, Promotes Nonsense-Mediated mRNA Decay at Two Distinct Steps

Authors
Journal
Molecular Cell
1097-2765
Publisher
Elsevier
Publication Date
Volume
39
Issue
3
Identifiers
DOI: 10.1016/j.molcel.2010.07.004
Keywords
  • Rna
  • Proteins
Disciplines
  • Biology

Abstract

Summary 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.

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