Computational analysis of candidate intron regulatory elements for tissue-specific alternative pre-mRNA splicing - PubMed (original) (raw)
Computational analysis of candidate intron regulatory elements for tissue-specific alternative pre-mRNA splicing
M Brudno et al. Nucleic Acids Res. 2001.
Abstract
Alternative pre-mRNA splicing is a major cellular process by which functionally diverse proteins can be generated from the primary transcript of a single gene, often in tissue-specific patterns. The current study investigates the hypothesis that splicing of tissue-specific alternative exons is regulated in part by control sequences in adjacent introns and that such elements may be recognized via computational analysis of exons sharing a highly specific expression pattern. We have identified 25 brain-specific alternative cassette exons, compiled a dataset of genomic sequences encompassing these exons and their adjacent introns and used word contrast algorithms to analyze key features of these nucleotide sequences. By comparison to a control group of constitutive exons, brain-specific exons were often found to possess the following: divergent 5' splice sites; highly pyrimidine-rich upstream introns; a paucity of GGG motifs in the downstream intron; a highly statistically significant over-representation of the hexanucleotide UGCAUG in the proximal downstream intron. UGCAUG was also found at a high frequency downstream of a smaller group of muscle-specific exons. Intriguingly, UGCAUG has been identified previously in a few intron splicing enhancers. Our results indicate that this element plays a much wider role than previously appreciated in the regulated tissue-specific splicing of many alternative exons.
Figures
Figure 1
Distribution of UGCAUG elements in flanking introns downstream and upstream of constitutive exons (control) and brain-specific exons (data). The frequency of occurrence of UGCAUG in each 100 nt interval of the introns is shown.
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References
- Hanke J., Brett,D., Zastrow,I., Aydin,A., Delbruck,S., Lehmann,G., Luft,F., Reich,J. and Bork,P. (1999) Alternative splicing of human genes: more the rule than the exception? Trends Genet., 15, 389–390. - PubMed
- Lopez A.J. (1998) Alternative splicing of pre-mRNA: developmental consequences and mechanisms of regulation. Annu. Rev. Genet., 32, 279–305. - PubMed
- Smith C.W. and Valcarcel,J. (2000) Alternative pre-mRNA splicing: the logic of combinatorial control. Trends Biochem. Sci., 25, 381–388. - PubMed
- Missler M. and Sudhof,T.C. (1998) Neurexins: three genes and 1001 products. Trends Genet., 14, 20–26. - PubMed
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