RESCUE-ESE identifies candidate exonic splicing enhancers in vertebrate exons - PubMed (original) (raw)

. 2004 Jul 1;32(Web Server issue):W187-90.

doi: 10.1093/nar/gkh393.

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RESCUE-ESE identifies candidate exonic splicing enhancers in vertebrate exons

William G Fairbrother et al. Nucleic Acids Res. 2004.

Abstract

A typical gene contains two levels of information: a sequence that encodes a particular protein and a host of other signals that are necessary for the correct expression of the transcript. While much attention has been focused on the effects of sequence variation on the amino acid sequence, variations that disrupt gene processing signals can dramatically impact gene function. A variation that disrupts an exonic splicing enhancer (ESE), for example, could cause exon skipping which would result in the exclusion of an entire exon from the mRNA transcript. RESCUE-ESE, a computational approach used in conjunction with experimental validation, previously identified 238 candidate ESE hexamers in human genes. The RESCUE-ESE method has recently been implemented in three additional species: mouse, zebrafish and pufferfish. Here we describe an online ESE analysis tool (http://genes.mit.edu/burgelab/rescue-ese/) that annotates RESCUE-ESE hexamers in vertebrate exons and can be used to predict splicing phenotypes by identifying sequence changes that disrupt or alter predicted ESEs.

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Figures

Figure 1

Figure 1

ESE hexamers for the 3′ss and the 5′ss have been clustered into 10 distinct motifs. The RESCUE-ESE protocol identified (A) 103 hexamers from the 5′ss and (B) 198 hexamers from the 3′ss which, when clustered on the basis of sequence similarity (penalizing 1 point for a mismatch or shift), could be aligned to form five ESE motifs for the 5′ss and eight motifs for the 3′ss. The dissimilarity between hexamers (or average dissimilarity between clusters of hexamers) is shown on the bottom scale, where the blue line represents the threshold dissimilarity of 2.7 that was used to define the clusters. The weight matrices that define the ESE motifs are represented as pictograms where the size of each letter is proportional to the nucleotide frequency for each of the 7–10 positions in the ESE motif.

Figure 2

Figure 2

The RESCUE-ESE web server. An exon skipping mutation from the human HPRT gene was analyzed by RESCUE-ESE. (A) Multi FASTA format files containing the wild type and mutant sequences of an A to T mutation at HPRT position 163 were pasted into the input window on the entry page of

http://genes.mit.edu/burgelab/rescue-ese

. (B) Species buttons allow the user to select from multiple sets of RESCUE-ESE hexamers. The output displays the input sequence with the ESEs drawn above in yellow. Additional links include ESE references, the original RESCUE-ESE paper and download options for ESE hexamers.

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References

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