Predictive identification of exonic splicing enhancers in human genes
Predictive identification of exonic splicing enhancers in human genes
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DOI：
10.1126/science.1073774
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发表时间：
2002-08-09
期刊：
影响因子：
56.9
通讯作者：
Burge, CB
中科院分区：
文献类型：
--
作者：
Fairbrother, WG;Yeh, RF;Burge, CB
外显子中存在的特定短寡核苷酸序列可增强前体mRNA的剪接，被称为外显子剪接增强子（ESEs），在组成性剪接和选择性剪接中发挥重要作用。开发了一种计算方法RESCUE - ESE，通过对外显子 - 内含子和剪接位点组成的统计分析来预测哪些序列具有ESE活性。当使用大量人类基因序列数据集时，该方法鉴定出10个预测的ESE基序。发现所有10个基序的代表在体内都显示出增强子活性，而这些序列的点突变体活性则大幅降低。所鉴定的基序能够预测人类基因中外显子突变的剪接表型。
Specific short oligonucleotide sequences that enhance pre-mRNA splicing when present in exons, termed exonic splicing enhancers (ESEs), play important roles in constitutive and alternative splicing. A computational method, RESCUE-ESE, was developed that predicts which sequences have ESE activity by statistical analysis of exon-intron and splice site composition. When large data sets of human gene sequences were used, this method identified 10 predicted ESE motifs. Representatives of all 10 motifs were found to display enhancer activity in vivo, whereas point mutants of these sequences exhibited sharply reduced activity. The motifs identified enable prediction of the splicing phenotypes of exonic mutations in human genes.