Failsafe nonsense-mediated mRNA decay does not detectably target eIF4E-bound mRNA

Daiki Matsuda, Nao Hosoda, Yoon Ki Kim, Lynne E. Maquat

Research output: Contribution to journalArticlepeer-review

40 Citations (Scopus)


Nonsense-mediated mRNA decay (NMD) generally eliminates messenger RNAs that prematurely terminate translation and occurs in all eukaryotes that have been studied, although with mechanistic variations. In mammals, NMD seems to be restricted to newly synthesized mRNA that is bound by the cap-binding heterodimer CBP80-CBP20 (CBP80/20) and typically has at least one exon junction complex (EJC) situated downstream of the nonsense codon and added post-splicing. However, mammalian NMD can also target spliced mRNA lacking an EJC downstream of the nonsense codon. Here we provide evidence that this additional pathway, known as failsafe NMD, likewise seems to be restricted to CBP80/20-bound mRNA and does not detectably target its subsequently remodeled product, eIF4E-bound mRNA. Our studies, including analyses of factor dependence, reveal important shared features of the two mammalian-cell NMD pathways as well as fundamental differences between NMD in mammals and Saccharomyces cerevisiae.

Original languageEnglish
Pages (from-to)974-979
Number of pages6
JournalNature Structural and Molecular Biology
Issue number10
Publication statusPublished - 2007 Oct

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology


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