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
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DOI：
10.1038/nsmb.2001
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发表时间：
2011-04-01
影响因子：
16.8
通讯作者：
Allain, Frederic H-T
中科院分区：
文献类型：
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作者：
Clery, Antoine;Jayne, Sandrine;Allain, Frederic H-T
Tra 2-β 1是一种独特的剪接因子，因为其单个RNA识别基序（RRM）位于两个RS（丝氨酸-丝氨酸）结构域之间。为了了解这种蛋白质如何识别其RNA靶标，我们解决了Tra 2-beta 1 RRM与RNA复合的结构。中心5 '-AGAA-3'基序被来自RRM的β折叠的残基和来自RRM两侧末端的残基特异性识别。该结构表明Tra 2-β 1的RNA结合诱导两个RS结构域相对于彼此的定位。通过检测Tra 2-β 1和RNA突变对SMN 2外显子7剪接的影响，我们验证了在结构中观察到的RNA-蛋白质接触对Tra 2-β 1功能的重要性，并确定了SMN 2外显子7中Tra 2-β 1的功能序列。最后，我们提出了一个模型的装配多个RNA结合蛋白的外显子。
Tra2-beta 1 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-beta 1 RRM in complex with RNA. The central 5'-AGAA-3' motif is specifically recognized by residues from the beta-sheet of the RRM and by residues from both extremities flanking the RRM. The structure suggests that RNA binding by Tra2-beta 1 induces positioning of the two RS domains relative to one another. By testing the effect of Tra2-beta 1 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-beta 1 and determined the functional sequence of Tra2-beta 1 in SMN2 exon 7. Finally, we propose a model for the assembly of multiple RNA binding proteins on this exon.