Structure of the Y14-Magoh core of the exon junction complex.
BACKGROUND
Splicing of pre-mRNA in eukaryotes imprints the resulting mRNA with a specific multiprotein complex, the exon-exon junction complex (EJC), at the sites of intron removal. The proteins of the EJC, Y14, Magoh, Aly/REF, RNPS1, Srm160, and Upf3, play critical roles in postsplicing processing, including nuclear export and cytoplasmic localization of the mRNA, and the nonsense-mediated mRNA decay (NMD) surveillance process. Y14 and Magoh are of particular interest because they remain associated with the mRNA in the same position after its export to the cytoplasm and require translation of the mRNA for removal. This tenacious, persistent, splicing-dependent, yet RNA sequence-independent, association suggests an important signaling function and must require distinct structural features for these proteins.


RESULTS
We describe the high-resolution structure and biochemical properties of the highly conserved human Y14 and Magoh proteins. Magoh has an unusual structure comprised of an extremely flat, six-stranded anti-parallel beta sheet packed against two helices. Surprisingly, Magoh binds with high affinity to the RNP motif RNA binding domain (RBD) of Y14 and completely masks its RNA binding surface.


CONCLUSIONS
The structure and properties of the Y14-Magoh complex suggest how the pre-mRNA splicing machinery might control the formation of a stable EJC-mRNA complex at splice junctions.
Lau
Chi-Kong
CK
Howard Hughes Medical Institute and Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6059, USA.
Diem
Michael D
MD
Dreyfuss
Gideon
G
Van Duyne
Gregory D
GD
D000595:Amino Acid Sequence; D002845:Chromatography; D002874:Chromosome Mapping; D003461:Crystallography; D004591:Electrophoresis, Polyacrylamide Gel; D005091:Exons / Q000502:physiology*; D031541:Fluorescence Resonance Energy Transfer; D015870:Gene Expression; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism*; D011485:Protein Binding; D017433:Protein Structure, Secondary; D012333:RNA, Messenger / Q000378:metabolism* / Q000502:physiology; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*
C491494:MAGOH protein, human; D009687:Nuclear Proteins; C406243:RBM8A protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins