UPF1 association with the cap-binding protein, CBP80, promotes nonsense-mediated mRNA decay at two distinct steps

Jungwook Hwang, Hanae Sato, Yalan Tang, Daiki Matsuda, Lynne E. Maquat

Research output: Contribution to journalArticle

71 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)396-409
Number of pages14
JournalMolecular Cell
Volume39
Issue number3
DOIs
StatePublished - Aug 2010
Externally publishedYes

Fingerprint

RNA Cap-Binding Proteins
Nonsense Mediated mRNA Decay
Nonsense Codon
Messenger RNA
Mammals
Exons
Proteins

Keywords

  • Proteins
  • RNA

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

UPF1 association with the cap-binding protein, CBP80, promotes nonsense-mediated mRNA decay at two distinct steps. / Hwang, Jungwook; Sato, Hanae; Tang, Yalan; Matsuda, Daiki; Maquat, Lynne E.

In: Molecular Cell, Vol. 39, No. 3, 08.2010, p. 396-409.

Research output: Contribution to journalArticle

Hwang, Jungwook ; Sato, Hanae ; Tang, Yalan ; Matsuda, Daiki ; Maquat, Lynne E. / UPF1 association with the cap-binding protein, CBP80, promotes nonsense-mediated mRNA decay at two distinct steps. In: Molecular Cell. 2010 ; Vol. 39, No. 3. pp. 396-409.
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