Mutuallv exclusive splicing of the insect Dscam Pre-mRNA directed by competing intronic RNA secondary structures
Mutuallv exclusive splicing of the insect Dscam Pre-mRNA directed by competing intronic RNA secondary structures
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DOI：
10.1016/j.cell.2005.07.028
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发表时间：
2005-10-07
期刊：
影响因子：
64.5
通讯作者：
Graveley, BR
中科院分区：
文献类型：
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作者：
Graveley, BR
果蝇DSCAM通过95个变量外显子的相互排斥替代剪接编码38,016个不同的轴突引导受体。重要的是，确保互斥外显子的互斥剪接的已知机制无法解释DSCAM中的这种现象。我已经确定了DSCAM外显子6群集中的两类保守元素，其中包含48个替代外显子 - 对接位点，该位点位于构型外显子5的内部和selector序列，该序列位于每个外显子6变体的上游。令人惊讶的是，每个选择器序列都与对接位点的一部分互补，并且该配对将一个和一个替代外显子与上游本构外显子置。对接位点的相互排斥性质：选择器序列相互作用表明这些竞争RNA结构的形成是该机制的核心组成部分，确保每个DSCAM mRNA中只包含一个外显子6变体。
Drosophila Dscam encodes 38,016 distinct axon guidance receptors through the mutually exclusive alternative splicing of 95 variable exons. Importantly, known mechanisms that ensure the mutually exclusive splicing of pairs of exons cannot explain this phenomenon in Dscam. I have identified two classes of conserved elements in the Dscam exon 6 cluster, which contains 48 alternative exons-the docking site, located in the intron downstream of constitutive exon 5, and the selector sequences, which are located upstream of each exon 6 variant. Strikingly, each selector sequence is complementary to a portion of the docking site, and this pairing juxtaposes one, and only one, alternative exon to the upstream constitutive exon. The mutually exclusive nature of the docking site:selector sequence interactions suggests that the formation of these competing RNA structures is a central component of the mechanism guaranteeing that only one exon 6 variant is included in each Dscam mRNA.