PMID:12881430

Citation	Gatfield, D, Unterholzner, L, Ciccarelli, FD, Bork, P and Izaurralde, E (2003) Nonsense-mediated mRNA decay in Drosophila: at the intersection of the yeast and mammalian pathways. EMBO J. 22:3960-70
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.
Links	PubMed PMC169044 Online version:10.1093/emboj/cdg371
Keywords	Amino Acid Sequence; Animals; Base Sequence; DNA Primers; Drosophila/genetics; Drosophila/metabolism; Drosophila Proteins/genetics; Drosophila Proteins/metabolism; Exons; Genes, Reporter; Hydrolysis; Molecular Sequence Data; Protein-Serine-Threonine Kinases/genetics; Protein-Serine-Threonine Kinases/metabolism; RNA, Messenger/genetics; RNA, Messenger/metabolism; Saccharomyces cerevisiae/genetics; Saccharomyces cerevisiae/metabolism; Sequence Homology, Amino Acid
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
DROME:Q6AWQ1	part_of	GO:0035145: exon-exon junction complex	ECO:0000304: author statement supported by traceable reference used in manual assertion		C		Seeded From UniProt	complete
DROME:SMG1	involved_in	GO:0000184: nuclear-transcribed mRNA catabolic process, nonsense-mediated decay	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
DROME:Q86BS8	involved_in	GO:0000184: nuclear-transcribed mRNA catabolic process, nonsense-mediated decay	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
DROME:Q8MZI0	involved_in	GO:0000184: nuclear-transcribed mRNA catabolic process, nonsense-mediated decay	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
DROME:Q8T080	involved_in	GO:0000184: nuclear-transcribed mRNA catabolic process, nonsense-mediated decay	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
DROME:Q95TL1	involved_in	GO:0000184: nuclear-transcribed mRNA catabolic process, nonsense-mediated decay	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
DROME:Q9V414	involved_in	GO:0000184: nuclear-transcribed mRNA catabolic process, nonsense-mediated decay	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
DROME:Q9VBZ6	involved_in	GO:0000184: nuclear-transcribed mRNA catabolic process, nonsense-mediated decay	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
DROME:Q9VU43	part_of	GO:0035145: exon-exon junction complex	ECO:0000304: author statement supported by traceable reference used in manual assertion		C		Seeded From UniProt	complete

References

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