Computational comparative analyses of alternative splicing regulation using full-length cDNA of various eukaryotes

Computational comparative analyses of alternative splicing regulation using full-length cDNA of various eukaryotes
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DOI:
10.1261/rna.5221604
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发表时间:
2004-07-01
期刊:
RNA
影响因子:
4.5
通讯作者:
Tomita, M
Tomita, M
中科院分区:
生物学3区
文献类型:
--
作者:
Itoh, H;Washio, T;Tomita, M

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我们以前报告了一种计算方法来推断选择性剪接模式从小家鼠全长cDNA克隆和微阵列数据。尽管我们预测了大量未报告的剪接变体,但调节选择性剪接的一般机制尚不清楚。在本研究中,我们比较了选择性外显子和组成性外显子的剪接位点强度和潜在的调控序列的频率。这些调控特征在五个不同的物种中进行了进一步的比较:智人,M。musculus、拟南芥、水稻和黑腹果蝇。我们的比较分析的坚实的统计学验证表明,替代外显子具有(1)较弱的剪接位点和(2)比组成型外显子更多的潜在调控序列。根据我们的观察,我们提出了一个组合模型的选择性剪接机制,这表明,选择性外显子含有弱剪接位点的潜在调控序列的外显子上的交替调节。
We previously reported a computational approach to infer alternative splicing patterns from Mus musculus full-length cDNA clones and microarray data. Although we predicted a large number of unreported splice variants, the general mechanisms regulating alternative splicing were yet unknown. In the present study, we compared alternative exons and constitutive exons in terms of splice-site strength and frequency of potential regulatory sequences. These regulatory features were further compared among five different species: Homo sapiens, M. musculus, Arabidopsis thaliana, Oryza sativa, and Drosophila melanogaster. Solid statistical validations of our comparative analyses indicated that alternative exons have (1) weaker splice sites and (2) more potential regulatory sequences than constitutive exons. Based on our observations, we propose a combinatorial model of alternative splicing mechanisms, which suggests that alternative exons contain weak splice sites regulated alternatively by potential regulatory sequences on the exons.