Alternative splicing: global insights

Following the original reports of pre-mRNA splicing in 1977, it was quickly realized that splicing together of different combinations of splice sites--alternative splicing--allows individual genes to generate more than one mRNA isoform. The full extent of alternative splicing only began to be revealed once large-scale genome and transcriptome sequencing projects began, rapidly revealing that alternative splicing is the rule rather than the exception. Recent technical innovations have facilitated the investigation of alternative splicing at a global scale. Splice-sensitive microarray platforms and deep sequencing allow quantitative profiling of very large numbers of alternative splicing events, whereas global analysis of the targets of RNA binding proteins reveals the regulatory networks involved in post-transcriptional gene control. Combined with sophisticated computational analysis, these new approaches are beginning to reveal the so-called 'RNA code' that underlies tissue and developmentally regulated alternative splicing, and that can be disrupted by disease-causing mutations.