Grosso Ana Rita, Gomes Anita Q, Barbosa-Morais Nuno L, Caldeira Sandra, Thorne Natalie P, Grech Godfrey, von Lindern Marieke, Carmo-Fonseca Maria
Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal.
Nucleic Acids Res. 2008 Sep;36(15):4823-32. doi: 10.1093/nar/gkn463. Epub 2008 Jul 24.
The alternative splicing code that controls and coordinates the transcriptome in complex multicellular organisms remains poorly understood. It has long been argued that regulation of alternative splicing relies on combinatorial interactions between multiple proteins, and that tissue-specific splicing decisions most likely result from differences in the concentration and/or activity of these proteins. However, large-scale data to systematically address this issue have just recently started to become available. Here we show that splicing factor gene expression signatures can be identified that reflect cell type and tissue-specific patterns of alternative splicing. We used a computational approach to analyze microarray-based gene expression profiles of splicing factors from mouse, chimpanzee and human tissues. Our results show that brain and testis, the two tissues with highest levels of alternative splicing events, have the largest number of splicing factor genes that are most highly differentially expressed. We further identified SR protein kinases and small nuclear ribonucleoprotein particle (snRNP) proteins among the splicing factor genes that are most highly differentially expressed in a particular tissue. These results indicate the power of generating signature-based predictions as an initial computational approach into a global view of tissue-specific alternative splicing regulation.
在复杂的多细胞生物中，控制和协调转录组的可变剪接密码仍未得到充分理解。长期以来，人们一直认为可变剪接的调控依赖于多种蛋白质之间的组合相互作用，并且组织特异性剪接决定很可能源于这些蛋白质浓度和/或活性的差异。然而，用于系统解决这一问题的大规模数据直到最近才开始可用。在这里，我们表明可以识别出反映可变剪接的细胞类型和组织特异性模式的剪接因子基因表达特征。我们使用一种计算方法来分析来自小鼠、黑猩猩和人类组织的基于微阵列的剪接因子基因表达谱。我们的结果表明，大脑和睾丸这两个具有最高可变剪接事件水平的组织，拥有数量最多的差异表达最为显著的剪接因子基因。我们还在特定组织中差异表达最为显著的剪接因子基因中，进一步鉴定出了SR蛋白激酶和小核核糖核蛋白颗粒（snRNP）蛋白。这些结果表明，生成基于特征的预测作为一种初步计算方法，对于全面了解组织特异性可变剪接调控具有重要作用。
