Human Splicing Finder: an online bioinformatics tool to predict splicing signals

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Desmet, F.-O. ; Hamroun, D. ; Lalande, M. ; Collod-Beroud, G. ; Claustres, M. ; Beroud, C. (2009)
  • Publisher: Oxford University Press
  • Journal: Nucleic Acids Research, volume 37, issue 9, pages e67-e67 (issn: 1362-4962, eissn: 1362-4962)
  • Related identifiers: doi: 10.1093/nar/gkp215, pmc: PMC2685110
  • Subject: Methods Online | [ SDV.GEN ] Life Sciences [q-bio]/Genetics | [SDV.GEN] Life Sciences [q-bio]/Genetics

International audience; Thousands of mutations are identified yearly. Although many directly affect protein expression, an increasing proportion of mutations is now believed to influence mRNA splicing. They mostly affect existing splice sites, but synonymous, non-synonymous or nonsense mutations can also create or disrupt splice sites or auxiliary cis-splicing sequences. To facilitate the analysis of the different mutations, we designed Human Splicing Finder (HSF), a tool to predict the effects of mutations on splicing signals or to identify splicing motifs in any human sequence. It contains all available matrices for auxiliary sequence prediction as well as new ones for binding sites of the 9G8 and Tra2-beta Serine-Arginine proteins and the hnRNP A1 ribonucleoprotein. We also developed new Position Weight Matrices to assess the strength of 5' and 3' splice sites and branch points. We evaluated HSF efficiency using a set of 83 intronic and 35 exonic mutations known to result in splicing defects. We showed that the mutation effect was correctly predicted in almost all cases. HSF could thus represent a valuable resource for research, diagnostic and therapeutic (e.g. therapeutic exon skipping) purposes as well as for global studies, such as the GEN2PHEN European Project or the Human Variome Project.
  • References (103)
    103 references, page 1 of 11

    1. Berget,S.M., Moore,C. and Sharp,P.A. (1977) Spliced segments at the 50 terminus of adenovirus 2 late mRNA. Proc. Natl Acad. Sci. USA, 74, 3171-3175.

    2. Nilsen,T.W. (2003) The spliceosome: the most complex macromolecular machine in the cell? Bioessays, 25, 1147-1149.

    3. Zhou,Z., Licklider,L.J., Gygi,S.P. and Reed,R. (2002) Comprehensive proteomic analysis of the human spliceosome. Nature, 419, 182-185.

    4. Breitbart,R.E., Nguyen,H.T., Medford,R.M., Destree,A.T., Mahdavi,V. and Nadal-Ginard,B. (1985) Intricate combinatorial patterns of exon splicing generate multiple regulated troponin T isoforms from a single gene. Cell, 41, 67-82.

    5. Maniatis,T. and Tasic,B. (2002) Alternative pre-mRNA splicing and proteome expansion in metazoans. Nature, 418, 236-243.

    6. Cartegni,L., Chew,S.L. and Krainer,A.R. (2002) Listening to silence and understanding nonsense: exonic mutations that affect splicing. Nat. Rev. Genet., 3, 285-298.

    7. Robberson,B.L., Cote,G.J. and Berget,S.M. (1990) Exon definition may facilitate splice site selection in RNAs with multiple exons. Mol. Cell Biol., 10, 84-94.

    8. Jacob,M. and Gallinaro,H. (1989) The 50 splice site: phylogenetic evolution and variable geometry of association with U1RNA. Nucleic Acids Res., 17, 2159-2180.

    9. Blencowe,B.J. (2000) Exonic splicing enhancers: mechanism of action, diversity and role in human genetic diseases. Trends Biochem Sci., 25, 106-110.

    10. Zhu,J., Mayeda,A. and Krainer,A.R. (2001) Exon identity established through differential antagonism between exonic splicing silencer-bound hnRNP A1 and enhancer-bound SR proteins. Mol. Cell, 8, 1351-1361.

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