Sequence motifs predictive of tissue-specific skipping

Abstract

Alternative splicing plays a major role in protein diversity and regulating gene expression. Motifs that regulate tissue-specific alternative splicing have been identified by groups studying small sets of genes. We introduce a tissue-specific skipping score for skipped exons using exon-exon junction microarray data. We compare these exons with known literature-verified EST skipped exons and exons predicted to be skipped in both human and mouse. After deriving tissue-specific skipped exon sets for brain, heart, muscle and testis, we find sequence features in the exon and flanking introns that distinguish these tissue-specific skipped exons from constitutive exons. Lastly, we use sequence-based scoring based on these features to predict tissue-specific skipped exons and compare these with EST data to demonstrate the tissue-specificity of the motifs.