SMG7 acts as a molecular link between mRNA surveillance and mRNA decay

Leonie Unterholzner, Elisa Izaurralde

    Research output: Contribution to journalArticle

    203 Citations (Scopus)

    Abstract

    Nonsense-mediated mRNA decay (NMD) is a surveillance mechanism that eliminates mRNAs containing premature termination codons (PTCs). The proteins UPF1, SMG5, SMG6, and SMG7 are essential NMD factors in metazoa. SMG5 and SMG7 form a complex with UPF1 and interact with each other via their N-terminal domains. Here we show that SMG5 and SMG7 colocalize in cytoplasmic mRNA decay bodies, while SMG6 forms separate cytoplasmic foci. When SMG7 is tethered to a reporter transcript, it elicits its degradation, bypassing the requirement for a PTC, UPF1, SMG5, or SMG6. This activity is mediated by the C-terminal domain of SMG7. In contrast, SMG5 requires SMG7 to trigger mRNA decay and to localize to decay bodies. Our findings indicate that SMG7 provides a link between the NMD and the mRNA degradation machinery by interacting with SMG5 and UPF1 via its N-terminal domain and targeting bound transcripts for decay via its C-terminal domain.
    Original languageEnglish
    Pages (from-to)587-96
    Number of pages10
    JournalMolecular Cell
    Volume16
    Issue number4
    DOIs
    Publication statusPublished - 19 Nov 2004

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