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PMID:14968132

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Citation

Bono, F, Ebert, J, Unterholzner, L, Güttler, T, Izaurralde, E and Conti, E (2004) Molecular insights into the interaction of PYM with the Mago-Y14 core of the exon junction complex. EMBO Rep. 5:304-10

Abstract

The exon junction complex (EJC) is deposited on mRNAs as a consequence of splicing and influences postsplicing mRNA metabolism. The Mago-Y14 heterodimer is a core component of the EJC. Recently, the protein PYM has been identified as an interacting partner of Mago-Y14. Here we show that PYM is a cytoplasmic RNA-binding protein that is excluded from the nucleus by Crm1. PYM interacts directly with Mago-Y14 by means of its N-terminal domain. The crystal structure of the Drosophila ternary complex at 1.9 A resolution reveals that PYM binds Mago and Y14 simultaneously, capping their heterodimerization interface at conserved surface residues. Formation of this ternary complex is also observed with the human proteins. Mago residues involved in the interaction with PYM have been implicated in nonsense-mediated mRNA decay (NMD). Consistently, human PYM is active in NMD tethering assays. Together, these data suggest a role for PYM in NMD.

Links

PubMed PMC1299003 Online version:10.1038/sj.embor.7400091

Keywords

Amino Acid Sequence; Animals; Conserved Sequence; Crystallography, X-Ray; Cytosol/metabolism; Dimerization; Drosophila Proteins/chemistry; Drosophila Proteins/genetics; Drosophila Proteins/metabolism; Electrophoretic Mobility Shift Assay; HeLa Cells; Humans; Immunochemistry; Molecular Sequence Data; Nuclear Proteins/chemistry; Nuclear Proteins/metabolism; Protein Binding; Protein Interaction Mapping; Protein Structure, Tertiary; RNA Splicing; RNA Stability; RNA-Binding Proteins/chemistry; RNA-Binding Proteins/genetics; RNA-Binding Proteins/metabolism; Sequence Alignment

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

DROME:MGN

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9V535

F

Seeded From UniProt

complete

DROME:MGN

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P82804

F

Seeded From UniProt

complete

DROME:PYM

located_in

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DROME:PYM

enables

GO:0003723: RNA binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

DROME:PYM

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P49028

F

Seeded From UniProt

complete

DROME:PYM

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9V535

F

Seeded From UniProt

complete

DROME:PYM

part_of

GO:0035145: exon-exon junction complex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DROME:RBM8A

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P49028

F

Seeded From UniProt

complete

DROME:RBM8A

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P82804

F

Seeded From UniProt

complete


See also

References

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