Yeo, G., Holste, D., Kreiman, G., and Burge, C

Variation in alternative splicing across human tissues

Genome Biology 5:R74 (2004) PDF

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Background: Alternative pre-mRNA splicing (AS) is widely used to generate different protein isoforms in specific cell or tissue types. To compare AS events across human tissues, we analyzed the splicing patterns of genomically-aligned ESTs derived from libraries of cDNAs from different tissues.
Results: Controlling for differences in EST coverage among tissues, we found that the brain and testis had the highest levels of exon skipping. The most pronounced differences between tissues were seen for the frequencies of alternative 3' splice site and alternative 5' splice site usage, which were ~50% to 100% higher in the liver than in any other human tissue studied. Quantitating differences in splice junction usage, the brain, pancreas, liver, and the peripheral nervous system had the most distinctive patterns of AS. Analysis of available microarray expression data showed that the liver had the most divergent pattern of expression of serine-argininge (SR) protein and hnRNP protein genes compared to the other human tissues studied, possibly contributing to the unusually high frequency of alternative splice site usage seen in this tissue. Sequence motifs enriched in alternative exons expressed in the brain, testis and liver suggest specific splicing factors that may be important in AS regulation in these tissues.
Conclusions: This study distinguishes the human brain, testis and liver as having unusually high levels of AS, highlights differences in the types of AS occurring commonly in different tissues, and identifies candidate cis-regulatory elements and trans-factors likely to play important roles in tissue-specific AS in human cells.