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Published Online July 11, 2002
Science DOI: 10.1126/science.1073774

Reports

Submitted on May 9, 2002
Accepted on July 2, 2002

Predictive Identification of Exonic Splicing Enhancers in Human Genes

William G. Fairbrother 1, Ru-Fang Yeh 2, Phillip A. Sharp 1, Christopher B. Burge 2*

1 Department of Biology, Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
2 Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

* To whom correspondence should be addressed. E-mail: cburge{at}mit.edu.

Specific short oligonucleotide sequences that enhance pre-mRNA splicing when present in exons, termed exonic splicing enhancers (ESEs), play important roles in constitutive and alternative splicing. A computational method was developed, RESCUE-ESE, that predicts which sequences have ESE activity by statistical analysis of exon-intron and splice site composition. When large datasets of human gene sequences were used, this method identified ten predicted ESE motifs. Representatives of all ten motifs were found to possess enhancer activity in vivo, whereas point mutants of these sequences exhibited sharply reduced activity. The motifs identified enable prediction of the splicing phenotypes of exonic mutations in human genes.


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