Nonsense-mediated mRNA decay in Drosophila

at the intersection of the yeast and mammalian pathways

David Gatfield, Leonie Unterholzner, Francesca D Ciccarelli, Peer Bork, Elisa Izaurralde

    Research output: Contribution to journalArticle

    205 Citations (Scopus)

    Abstract

    The nonsense-mediated mRNA decay (NMD) pathway promotes the rapid degradation of mRNAs containing premature stop codons (PTCs). In Caenorhabditis elegans, seven genes (smg1-7) playing an essential role in NMD have been identified. Only SMG2-4 (known as UPF1-3) have orthologs in Saccharomyces cerevisiae. Here we show that the Drosophila orthologs of UPF1-3, SMG1, SMG5 and SMG6 are required for the degradation of PTC-containing mRNAs, but that there is no SMG7 ortholog in this organism. In contrast, orthologs of SMG5-7 are encoded by the human genome and all three are required for NMD. In human cells, exon boundaries have been shown to play a critical role in defining PTCs. This role is mediated by components of the exon junction complex (EJC). Contrary to expectation, however, we show that the components of the EJC are dispensable for NMD in Drosophila cells. Consistently, PTC definition occurs independently of exon boundaries in Drosophila. Our findings reveal that despite conservation of the NMD machinery, different mechanisms have evolved to discriminate premature from natural stop codons in metazoa.
    Original languageEnglish
    Pages (from-to)3960-70
    Number of pages11
    JournalEMBO Journal
    Volume22
    Issue number15
    DOIs
    Publication statusPublished - 1 Aug 2003

    Fingerprint

    Nonsense Mediated mRNA Decay
    Nonsense Codon
    Yeast
    Drosophila
    Yeasts
    Exons
    Messenger RNA
    RNA Stability
    Caenorhabditis elegans
    Genes
    Human Genome
    Degradation
    Saccharomyces cerevisiae
    Machinery
    Conservation
    Cells

    Cite this

    Gatfield, D., Unterholzner, L., Ciccarelli, F. D., Bork, P., & Izaurralde, E. (2003). Nonsense-mediated mRNA decay in Drosophila: at the intersection of the yeast and mammalian pathways. EMBO Journal, 22(15), 3960-70. https://doi.org/10.1093/emboj/cdg371
    Gatfield, David ; Unterholzner, Leonie ; Ciccarelli, Francesca D ; Bork, Peer ; Izaurralde, Elisa. / Nonsense-mediated mRNA decay in Drosophila : at the intersection of the yeast and mammalian pathways. In: EMBO Journal. 2003 ; Vol. 22, No. 15. pp. 3960-70.
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    abstract = "The nonsense-mediated mRNA decay (NMD) pathway promotes the rapid degradation of mRNAs containing premature stop codons (PTCs). In Caenorhabditis elegans, seven genes (smg1-7) playing an essential role in NMD have been identified. Only SMG2-4 (known as UPF1-3) have orthologs in Saccharomyces cerevisiae. Here we show that the Drosophila orthologs of UPF1-3, SMG1, SMG5 and SMG6 are required for the degradation of PTC-containing mRNAs, but that there is no SMG7 ortholog in this organism. In contrast, orthologs of SMG5-7 are encoded by the human genome and all three are required for NMD. In human cells, exon boundaries have been shown to play a critical role in defining PTCs. This role is mediated by components of the exon junction complex (EJC). Contrary to expectation, however, we show that the components of the EJC are dispensable for NMD in Drosophila cells. Consistently, PTC definition occurs independently of exon boundaries in Drosophila. Our findings reveal that despite conservation of the NMD machinery, different mechanisms have evolved to discriminate premature from natural stop codons in metazoa.",
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    Gatfield, D, Unterholzner, L, Ciccarelli, FD, Bork, P & Izaurralde, E 2003, 'Nonsense-mediated mRNA decay in Drosophila: at the intersection of the yeast and mammalian pathways', EMBO Journal, vol. 22, no. 15, pp. 3960-70. https://doi.org/10.1093/emboj/cdg371

    Nonsense-mediated mRNA decay in Drosophila : at the intersection of the yeast and mammalian pathways. / Gatfield, David; Unterholzner, Leonie; Ciccarelli, Francesca D; Bork, Peer; Izaurralde, Elisa.

    In: EMBO Journal, Vol. 22, No. 15, 01.08.2003, p. 3960-70.

    Research output: Contribution to journalArticle

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