Research into alternative splicing

Outline

Our group has considerable interest in alternative splicing. We have shown 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 analyse 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. We have shown that the core spliceosomal machinery is generally conserved across the eukaryotic lineage and the repertoires of alternative splicing regulators in human and mouse are very similar

• Grosso AR, Gomes AQ, Barbosa-Morais NL, Caldeira S, Thorne NP, Grech G, von Lindern M, and Carmo-Fonseca M Tissue-specific splicing factor gene expression signatures. Nucleic Acids Res 2008 36, 4823-4832. [pubmed]
• Gama-Carvalho M, Barbosa-Morais NL, Brodsky AS, Silver PA, and Carmo-Fonseca M Genome-wide identification of functionally distinct subsets of cellular mRNAs associated with two nucleocytoplasmic-shuttling mammalian splicing factors. Genome Biol 2006 7, R113. [pubmed]
• Mollet I, Barbosa-Morais NL, Andrade J, and Carmo-Fonseca M. Diversity of human U2AF splicing factors. FEBS J 2006 273, 4807-4816. [pubmed]