Variable window binding for mutually exclusive alternative splicing.
Variable window binding for mutually exclusive alternative splicing.
复制标题
可变窗口绑定，用于相互排斥的替代剪接。
DOI：
10.1186/gb-2006-7-1-r2
复制
发表时间：
2006
期刊：
影响因子：
12.3
通讯作者：
Varadan, Vinay
中科院分区：
文献类型：
--
作者：
Anastassiou, Dimitris;Liu, Hairuo;Varadan, Vinay
本文描述了果蝇Dscam基因外显子6的可变窗口结合机制，该机制代表了选择性剪接的极端情况。高级生物的基因经历选择性剪接，这可能是互斥的，从某种意义上说，只有一个外显子包含在成熟的mRNA中，而这些外显子通常排列在串联阵列中。然而，在许多情况下，潜在的生物学机制的细节是未知的。我们描述了“可变窗口结合”——一种用于互斥选择性剪接的机制，通过这种机制，果蝇Dscam基因前mrna中外显子6集群上游的保守核苷酸“锚定”序列的一个片段（“窗口”）与一个内含子结合，从而激活直接从结合位点下游的外显子选择。这一机制得到了一个事实的支持，即锚定序列可以通过使用遗传算法从内含子序列的比较中推断出来。由于每个外显子选择的窗口位置不同，因此可以通过阻断该序列的一部分来实现调节。我们还描述了基于竞争前mrna茎环结构的相关机制，该机制可以解释Dscam基因外显子17的互斥选择。在比较序列分析的基础上，我们提出了果蝇Dscam基因选择性剪接的有效生物学机制，该机制依赖于pre-mRNA的固有结构。利用“基因座控制区域”的相关机制可能涉及到外显子或基因互斥选择的其他场合。
A mechanism called Variable Window Binding for mutually exclusive alternative splicing is described for exon 6 of the Drosophila Dscam gene, which represents an extreme case of alternative splicing. Genes of advanced organisms undergo alternative splicing, which can be mutually exclusive, in the sense that only one exon is included in the mature mRNA out of a cluster of alternative choices, often arranged in a tandem array. In many cases, however, the details of the underlying biologic mechanisms are unknown. We describe 'variable window binding' - a mechanism used for mutually exclusive alternative splicing by which a segment ('window') of a conserved nucleotide 'anchor' sequence upstream of the exon 6 cluster in the pre-mRNA of the fruitfly Dscam gene binds to one of the introns, thereby activating selection of the exon directly downstream from the binding site. This mechanism is supported by the fact that the anchor sequence can be inferred solely from a comparison of the intron sequences using a genetic algorithm. Because the window location varies for each exon choice, regulation can be achieved by obstructing part of that sequence. We also describe a related mechanism based on competing pre-mRNA stem-loop structures that could explain the mutually exclusive choice of exon 17 of the Dscam gene. On the basis of comparative sequence analysis, we propose efficient biologic mechanisms of alternative splicing of the Drosophila Dscam gene that rely on the inherent structure of the pre-mRNA. Related mechanisms employing 'locus control regions' could be involved on other occasions of mutually exclusive choices of exons or genes.