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PMID:12881430

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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

Significance

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


See also

References

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