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.
Original language | English (US) |
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Pages (from-to) | 396-409 |
Number of pages | 14 |
Journal | Molecular Cell |
Volume | 39 |
Issue number | 3 |
DOIs | |
State | Published - Aug 2010 |
Externally published | Yes |
Keywords
- Proteins
- RNA
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology