Finding signals that regulate alternative splicing in the post-genomic era.docVIP

/2002/3/11/reviews/0008.1 Review Finding signals that regulate alternative splicing in the post- genomic era Andrea N Ladd and Thomas A Cooper Address: Department of Pathology, Baylor College of Medicine, Houston, TX 77030, USA. Correspondence: Thomas A Cooper. E-mail: tcooper@ Published: 23 October 2002 GenomeBiology 2002, 3(11):reviews0008.1–0008.16 The electronic version of this article is the complete one and can be found online at /2002/3/11/reviews/0008 ? BioMed Central Ltd (Print ISSN 1465-6906; Online ISSN 1465-6914) Abstract Alternative splicing of pre-mRNAs is central to the generation of diversity from the relatively small number of genes in metazoan genomes. Auxiliarycis elements andtrans-acting factors are required for the recognition of constitutive and alternatively spliced exons and their inclusion in pre-mRNA. Here, we discuss the regulatory elements that direct alternative splicing and how genome-wide analyses can aid in their identification. Alternative splicing, the process by which multiple mRNA isoforms are generated from a single pre-mRNA species, is an important means of regulating gene expression. Alterna- tive splicing determines cell fate in numerous contexts, such as sexual differentiation in Drosophila and apoptosis in mammals [1], and aberrant regulation of alternative splicing has been implicated in human disease [1,2]. Additional attention is now being given to alternative splicing in the wake of the sequencing of the human genome. On the basis of the initial drafts of the human genome sequence it was estimated that there are 30,000 to 40,000 genes [3,4] - sig- nificantly fewer than expected. Although final gene counts may be higher, there is a disparity between the relatively small number of human genes and the complexity of the human proteome. This suggests that alternative splicing is important in the generation of protein diversity. This article