A network of conserved co-occurring motifs for the regulation of alternative splicing.
Cis-acting short sequence motifs play important roles in alternative splicing. It is now possible to identify such sequence motifs as conserved sequence patterns in genome sequence alignments. Here, we report the systematic search for motifs in the neighboring introns of alternatively spliced exons by using comparative analysis of mammalian genome alignments. We identified 11 conserved sequence motifs that might be involved in the regulation of alternative splicing. These motifs are not only significantly overrepresented near alternatively spliced exons, but they also co-occur with each other, thus, forming a network of cis-elements, likely to be the basis for context-dependent regulation. Based on this finding, we applied the motif co-occurrence to predict alternatively skipped exons. We verified exon skipping in 29 cases out of 118 predictions (25%) by EST and mRNA sequences in the databases. For the predictions not verified by the database sequences, we confirmed exon skipping in 10 additional cases by using both RT-PCR experiments and the publicly available RNA-Seq data. These results indicate that even more alternative splicing events will be found with the progress of large-scale and high-throughput analyses for various tissue samples and developmental stages.
Suyama
Mikita
M
Structural and Computational Biology, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
Harrington
Eoghan D
ED
Vinokourova
Svetlana
S
von Knebel Doeberitz
Magnus
M
Ohara
Osamu
O
Bork
Peer
P
D017398:Alternative Splicing; D000818:Animals; D001483:Base Sequence; D017124:Conserved Sequence; D005091:Exons; D023281:Genomics; D006801:Humans; D007438:Introns; D008969:Molecular Sequence Data; D038621:Regulatory Sequences, Ribonucleic Acid; D016415:Sequence Alignment
D038621:Regulatory Sequences, Ribonucleic Acid