title: Tissue-specific splicing factor gene expression signatures.
abstract: 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.
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal.
authors.forename: Ana Rita
authors.initials: AR
authors.lastname: Grosso
authors.forename: Anita Q
authors.initials: AQ
authors.lastname: Gomes
authors.forename: Nuno L
authors.initials: NL
authors.lastname: Barbosa-Morais
authors.forename: Sandra
authors.initials: S
authors.lastname: Caldeira
authors.forename: Natalie P
authors.initials: NP
authors.lastname: Thorne
authors.forename: Godfrey
authors.initials: G
authors.lastname: Grech
authors.forename: Marieke
authors.initials: M
authors.lastname: von Lindern
authors.forename: Maria
authors.initials: M
authors.lastname: Carmo-Fonseca
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D019295:Computational Biology; D020869:Gene Expression Profiling; D006801:Humans; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D002679:Pan troglodytes / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D012333:RNA, Messenger; D016601:RNA-Binding Proteins