Context-dependent splicing regulation: exon definition, co-occurring motif pairs and tissue specificity.

Splicing is a crucial process in gene expression in higher organisms because: 1) most vertebrate genes contain introns; and 2) alternative splicing is primarily responsible for increasing proteomic complexity and functional diversity. Intron definition, the coordination across an intron, is a mandatory step in the splicing process. However, exon definition, the coordination across an exon, is also thought to be required for the splicing of most vertebrate exons. Recent investigations of exon definition complexes provide insights into splicing dynamics. That splicing regulators act in a context-dependent mode is supported by a large collection of evidence. Splicing contexts generally can be classified as cis-element and trans-element contexts. A widespread cis-element context is defined by co-occurring motif pairs to which splicing regulatory factors bind to direct specific molecular interactions. Splicing regulation is also coordinated by trans-element contexts as exemplified by tissue specific splicing, where alternative exons can be coordinately regulated by a few splicing factors, the expression and/or activity of which are concertedly higher or lower in the corresponding tissues.