The splicing regulatory element, UGCAUG, is phylogenetically and spatially conserved in introns that flank tissue-specific alternative exons
The splicing regulatory element, UGCAUG, is phylogenetically and spatially conserved in introns that flank tissue-specific alternative exons
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DOI：
10.1093/nar/gki210
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发表时间：
2005-01-01
影响因子：
14.9
通讯作者：
Conboy, JG
中科院分区：
文献类型：
--
作者：
Minovitsky, S;Gee, SL;Conboy, JG
先前的研究已确定 UGCAUG 是一种内含子剪接增强子，通常位于人类基因组中组织特异性替代外显子附近。在这里，我们证明 UGCAUG 在系统发育和空间上保守的内含子位于大脑丰富的替代外显子（从鱼到人）的侧面。对小鼠、大鼠、狗、鸡和河豚基因组的序列分析揭示了 UGCAUG 与大脑富集的替代外显子下游的近端内含子区域存在统计学上显着的关联。内含子 UGCAUG 元件的数量、位置和序列背景在哺乳动物和鸡中高度保守，但在鱼类中差异更大。控制数据集，包括组成型外显子和非组织特异性替代外显子，表现出紧密相连的 UGCAUG 元件的发生率要低得多。我们认为，UGCAUG 元件的高序列特异性及其与组织特异性替代外显子的独特关联，使其成为剪接开关机制的关键组成部分，该机制旨在激活细胞类型特异性模式中有限的剪接事件。我们进一步推测，与最近描述的 Fox-1 剪接因子相关的高度保守的 UGCAUG 结合蛋白在介导这种特异性中发挥着关键作用。
Previous studies have identified UGCAUG as an intron splicing enhancer that is frequently located adjacent to tissue-specific alternative exons in the human genome. Here, we show that UGCAUG is phylogenetically and spatially conserved in introns that flank brain-enriched alternative exons from fish to man. Analysis of sequence from the mouse, rat, dog, chicken and pufferfish genomes revealed a strongly statistically significant association of UGCAUG with the proximal intron region downstream of brain-enriched alternative exons. The number, position and sequence context of intronic UGCAUG elements were highly conserved among mammals and in chicken, but more divergent in fish. Control datasets, including constitutive exons and non-tissue-specific alternative exons, exhibited a much lower incidence of closely linked UGCAUG elements. We propose that the high sequence specificity of the UGCAUG element, and its unique association with tissue-specific alternative exons, mark it as a critical component of splicing switch mechanism(s) designed to activate a limited repertoire of splicing events in cell type-specific patterns. We further speculate that highly conserved UGCAUG-binding protein(s) related to the recently described Fox-1 splicing factor play a critical role in mediating this specificity.