Nonsense-mediated mRNA decay in Drosophila:at the intersection of the yeast and mammalian pathways

Jul 26, 2003The EMBO journal

How cells control faulty gene messages in fruit flies, combining features from yeast and mammals

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Abstract

Drosophila orthologs of UPF1-3 are essential for the degradation of mRNAs containing premature stop codons.

Seven genes involved in the nonsense-mediated mRNA decay (NMD) pathway have been identified in Caenorhabditis elegans.
Only UPF1-3 have orthologs in Saccharomyces cerevisiae, while Drosophila lacks an SMG7 ortholog.
In humans, orthologs of SMG5-7 are necessary for NMD.
Exon boundaries are crucial for defining premature stop codons in human cells.
In Drosophila, components of the exon junction complex (EJC) are not required for NMD.
PTC definition in Drosophila occurs independently of exon boundaries, indicating evolved differences in NMD mechanisms.

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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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Nonsense-mediated mRNA decay in Drosophila:at the intersection of the yeast and mammalian pathways

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