Molecular basis of purine-rich RNA recognition by the human SR-like protein Tra2-β1
Molecular basis of purine-rich RNA recognition by the human SR-like protein Tra2-β1
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.
- ETH Zurich Switzerland
- University of Leicester United Kingdom
- Institute of Molecular Biology and Biophysics Switzerland
- University of Kentucky United States
- University of Erlangen-Nuremberg Germany
Models, Molecular, Serine-Arginine Splicing Factors, Protein Conformation, Nuclear Magnetic Resonance, Molecular Sequence Data, Molecular, RNA-Binding Proteins, Nerve Tissue Proteins, 612, Cell Line, Survival of Motor Neuron 2 Protein, Models, Purines, Humans, RNA, Amino Acid Sequence, Nuclear Magnetic Resonance, Biomolecular, Biomolecular
Models, Molecular, Serine-Arginine Splicing Factors, Protein Conformation, Nuclear Magnetic Resonance, Molecular Sequence Data, Molecular, RNA-Binding Proteins, Nerve Tissue Proteins, 612, Cell Line, Survival of Motor Neuron 2 Protein, Models, Purines, Humans, RNA, Amino Acid Sequence, Nuclear Magnetic Resonance, Biomolecular, Biomolecular
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