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Science 9 August 2002:
Vol. 297. no. 5583, p. 893
DOI: 10.1126/science.297.5583.893n
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A combination of computational and experimental approaches has been used to identify exonic splicing enhancers (ESEs), which increase the joining of exons to build messenger RNA. Fairbrother et al. (p. 1007) started with fundamental attributes of ESEs to derive a set of hexamer candidates from human genomic sequences. Cluster analysis of more than 200 hexamers resulted in the identification of 10 distinct groups of hexamer motifs. Of these, five were different from known ESEs. Experimental testing revealed that all of the groups possessed ESE activity, albeit at different levels. Mutation of the individual ESEs that had been identified resulted in decreased ESE activity. A group of mutations that cause exon skipping in the human HPRT gene in vivo were found with sequences that fit within the authors' models of ESEs.




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Science. ISSN 0036-8075 (print), 1095-9203 (online)