Upf1 Phosphorylation Triggers Translational Repression during Nonsense-Mediated mRNA Decay

Olaf Isken, Yoon Ki Kim, Nao Hosoda, Greg L. Mayeur, J. W B Hershey, Lynne E. Maquat

Research output: Contribution to journalArticle

185 Citations (Scopus)

Abstract

In mammalian cells, nonsense-mediated mRNA decay (NMD) generally requires that translation terminates sufficiently upstream of a post-splicing exon junction complex (EJC) during a pioneer round of translation. The subsequent binding of Upf1 to the EJC triggers Upf1 phosphorylation. We provide evidence that phospho-Upf1 functions after nonsense codon recognition during steps that involve the translation initiation factor eIF3 and mRNA decay factors. Phospho-Upf1 interacts directly with eIF3 and inhibits the eIF3-dependent conversion of 40S/Met-tRNAiMet/mRNA to translationally competent 80S/Met-tRNAiMet/mRNA initiation complexes to repress continued translation initiation. Consistent with phospho-Upf1 impairing eIF3 function, NMD fails to detectably target nonsense-containing transcripts that initiate translation independently of eIF3 from the CrPV IRES. There is growing evidence that translational repression is a key transition that precedes mRNA delivery to the degradation machinery. Our results uncover a critical step during NMD that converts a pioneer translation initiation complex to a translationally compromised mRNP.

Original languageEnglish
Pages (from-to)314-327
Number of pages14
JournalCell
Volume133
Issue number2
DOIs
Publication statusPublished - 2008 Apr 18
Externally publishedYes

Fingerprint

Nonsense Mediated mRNA Decay
Phosphorylation
Messenger RNA
Exons
Peptide Initiation Factors
Nonsense Codon
RNA Stability
Machinery
Cells
Degradation

Keywords

  • PROTEINS
  • RNA

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Isken, O., Kim, Y. K., Hosoda, N., Mayeur, G. L., Hershey, J. W. B., & Maquat, L. E. (2008). Upf1 Phosphorylation Triggers Translational Repression during Nonsense-Mediated mRNA Decay. Cell, 133(2), 314-327. https://doi.org/10.1016/j.cell.2008.02.030

Upf1 Phosphorylation Triggers Translational Repression during Nonsense-Mediated mRNA Decay. / Isken, Olaf; Kim, Yoon Ki; Hosoda, Nao; Mayeur, Greg L.; Hershey, J. W B; Maquat, Lynne E.

In: Cell, Vol. 133, No. 2, 18.04.2008, p. 314-327.

Research output: Contribution to journalArticle

Isken, O, Kim, YK, Hosoda, N, Mayeur, GL, Hershey, JWB & Maquat, LE 2008, 'Upf1 Phosphorylation Triggers Translational Repression during Nonsense-Mediated mRNA Decay', Cell, vol. 133, no. 2, pp. 314-327. https://doi.org/10.1016/j.cell.2008.02.030
Isken, Olaf ; Kim, Yoon Ki ; Hosoda, Nao ; Mayeur, Greg L. ; Hershey, J. W B ; Maquat, Lynne E. / Upf1 Phosphorylation Triggers Translational Repression during Nonsense-Mediated mRNA Decay. In: Cell. 2008 ; Vol. 133, No. 2. pp. 314-327.
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