Institute for Molecular Biology and Biophysics, Swiss Federal Institute of Technology, Zürich, Switzerland.
Nat Struct Mol Biol. 2011 Apr;18(4):443-50. doi: 10.1038/nsmb.2001. Epub 2011 Mar 13.
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.
Tra2-β1 是一种独特的剪接因子，因为它的单个 RNA 识别基序（RRM）位于两个 RS（精氨酸-丝氨酸）结构域之间。为了了解该蛋白如何识别其 RNA 靶标，我们解析了 Tra2-β1 RRM 与 RNA 复合物的结构。中央 5'-AGAA-3' 基序是由 RRM 的β-折叠和 RRM 两侧的残基特异性识别的。该结构表明，Tra2-β1 通过 RNA 结合诱导两个 RS 结构域彼此相对定位。通过测试 Tra2-β1 和 RNA 突变对 SMN2 外显子 7 剪接的影响，我们验证了结构中观察到的 RNA-蛋白相互作用对于 Tra2-β1 功能的重要性，并确定了 Tra2-β1 在 SMN2 外显子 7 中的功能序列。最后，我们提出了一个关于多个 RNA 结合蛋白在该外显子上组装的模型。
