Molecular insights into the interaction of PYM with the Mago-Y14 core of the exon junction complex.
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.
Mesh Terms:
Amino Acid Sequence, Animals, Conserved Sequence, Crystallography, X-Ray, Cytosol, Dimerization, Drosophila Proteins, Electrophoretic Mobility Shift Assay, HeLa Cells, Humans, Immunochemistry, Molecular Sequence Data, Nuclear Proteins, Protein Binding, Protein Interaction Mapping, Protein Structure, Tertiary, RNA Splicing, RNA Stability, RNA-Binding Proteins, Sequence Alignment
Amino Acid Sequence, Animals, Conserved Sequence, Crystallography, X-Ray, Cytosol, Dimerization, Drosophila Proteins, Electrophoretic Mobility Shift Assay, HeLa Cells, Humans, Immunochemistry, Molecular Sequence Data, Nuclear Proteins, Protein Binding, Protein Interaction Mapping, Protein Structure, Tertiary, RNA Splicing, RNA Stability, RNA-Binding Proteins, Sequence Alignment
EMBO Rep.
Date: Mar. 01, 2004
PubMed ID: 14968132
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