title: Molecular basis of purine-rich RNA recognition by the human SR-like protein Tra2-β1.
abstract: Tra2-β1 is a unique splicing factor as its single RNA recognition motif (RRM) is located between two RS (arginine-serine) domains. To understand how this protein recognizes its RNA target, we solved the structure of Tra2-β1 RRM in complex with RNA. The central 5'-AGAA-3' motif is specifically recognized by residues from the β-sheet of the RRM and by residues from both extremities flanking the RRM. The structure suggests that RNA binding by Tra2-β1 induces positioning of the two RS domains relative to one another. By testing the effect of Tra2-β1 and RNA mutations on the splicing of SMN2 exon 7, we validated the importance of the RNA-protein contacts observed in the structure for the function of Tra2-β1 and determined the functional sequence of Tra2-β1 in SMN2 exon 7. Finally, we propose a model for the assembly of multiple RNA binding proteins on this exon.
authors.affiliation: Institute for Molecular Biology and Biophysics, Swiss Federal Institute of Technology, Zürich, Switzerland.
authors.forename: Antoine
authors.initials: A
authors.lastname: Cléry
authors.forename: Sandrine
authors.initials: S
authors.lastname: Jayne
authors.forename: Natalya
authors.initials: N
authors.lastname: Benderska
authors.forename: Cyril
authors.initials: C
authors.lastname: Dominguez
authors.forename: Stefan
authors.initials: S
authors.lastname: Stamm
authors.forename: Frédéric H-T
authors.initials: FH
authors.lastname: Allain
mesh_terms: D000595:Amino Acid Sequence; D002460:Cell Line; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019906:Nuclear Magnetic Resonance, Biomolecular; D011487:Protein Conformation; D011687:Purines / Q000378:metabolism*; D012313:RNA / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000068103:Serine-Arginine Splicing Factors; D055540:Survival of Motor Neuron 2 Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D009419:Nerve Tissue Proteins; D011687:Purines; D016601:RNA-Binding Proteins; C526477:SMN2 protein, human; D055540:Survival of Motor Neuron 2 Protein; C097083:TRA2B protein, human; D000068103:Serine-Arginine Splicing Factors; D012313:RNA