The alternative exon database (AEDB)

Presentation

telephone: +49 9131 8524622
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email: stefan@stamms-lab.net
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presenter: Stefan Stamm

Stefan Stamm, Peter Stoilov, and Michael Q. Zhang

We compiled a comprehensive database (AEDB) of alternative exons from the literature and analyzed them statistically. Most alternative exons are cassette exons and are expressed in more than two tissues. Of all exons whose expression was reported to be specific for a certain tissue, the majority was expressed in the brain. Whereas the length of constitutive exons follows a normal distribution, the distribution of alternative exons is skewed towards smaller ones. Furthermore, alternative splice sites deviate more from the consensus: their 3' splice sites are characterized by a higher purine content in the polypyrimidine stretch and their 5' splice sites deviate mostly at the +4 and +5 positions from the consensus sequence. Furthermore, for exons expressed in a single tissue, adenosine is more frequently used at the -3 position of the 3' splice site. These results confim our previous findings form neuron-specific exons. The usage of exons with suboptimal splice sites is stimulated by regulatory sequences known as exonic enhancers. SELEX eperiments and analysis of model systems shown that two major groups of enhancers exist: purine rich and AC-rich. In addition to those sequence elements, analysis using a Gibbs algorithm identifies several motifs in exons surrounded by weak splice sites and in tissue-specific exons. Those naturally exonic enhancer motifs are more degenerate than sequences obtained by SELEX. Together, these data indicate a combinatorial effect of weak splice sites, atypical nucleotide usage at certain positions and functional enhancers as an important contribution to alternative exon regulation.