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PMID: 14656968 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Validation Study

Sequence information for the splicing of human pre-mRNA identified by support vector machine classification.

Genome research ·Vol. 13 ·No. 12 ·2003-12-00 ·Pages 2637-50

Zhang XH, Heller KA, Hefter I, Leslie CS, Chasin LA

Abstract

Vertebrate pre-mRNA transcripts contain many sequences that resemble splice sites on the basis of agreement to the consensus,yet these more numerous false splice sites are usually completely ignored by the cellular splicing machinery. Even at the level of exon definition,pseudo exons defined by such false splices sites outnumber real exons by an order of magnitude. We used a support vector machine to discover sequence information that could be used to distinguish real exons from pseudo exons. This machine learning tool led to the definition of potential branch points,an extended polypyrimidine tract,and C-rich and TG-rich motifs in a region limited to 50 nt upstream of constitutively spliced exons. C-rich sequences were also found in a region extending to 80 nt downstream of exons,along with G-triplet motifs. In addition,it was shown that combinations of three bases within the splice donor consensus sequence were more effective than consensus values in distinguishing real from pseudo splice sites; two-way base combinations were optimal for distinguishing 3' splice sites. These data also suggest that interactions between two or more of these elements may contribute to exon recognition,and provide candidate sequences for assessment as intronic splicing enhancers.

MeSH Terms
Artificial Intelligence Base Composition Computational Biology/methods,statistics & numerical data Cytosine/metabolism Databases, Genetic Enhancer Elements, Genetic Exons Guanine/metabolism Humans Pyrimidines/metabolism RNA Precursors/classification,genetics RNA Splice Sites/genetics RNA Splicing/genetics Untranslated Regions/genetics
Chemicals
Pyrimidines RNA Precursors RNA Splice Sites Untranslated Regions Guanine Cytosine
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Zhang Xiang H-F
Department of Biological Sciences, Columbia University, New York, New York 10027, USA.
Heller Katherine A
Hefter Ilana
Leslie Christina S
Chasin Lawrence A
References (51)
51 references, click to expand
  1. EID: the Exon-Intron Database-an exhaustive database of protein-coding intron-containing genes.
    Nucleic Acids Res. 2000 Jan 1;28(1):185-90 PMID: 10592221
  2. Mutations that alter RNA splicing of the human HPRT gene: a review of the spectrum.
    Mutat Res. 1998 Nov;411(3):179-214 PMID: 9804951
  3. Characterization of human RNA splice signals by iterative functional selection of splice sites.
    RNA. 2000 Apr;6(4):528-44 PMID: 10786844
  4. Mechanisms of fidelity in pre-mRNA splicing.
    Curr Opin Cell Biol. 2000 Jun;12(3):340-5 PMID: 10801464
  5. A 5' splice site-proximal enhancer binds SF1 and activates exon bridging of a microexon.
    Mol Cell Biol. 2000 Jun;20(11):3988-95 PMID: 10805741
  6. Multiple splicing defects in an intronic false exon.
    Mol Cell Biol. 2000 Sep;20(17):6414-25 PMID: 10938119
  7. Human genomic sequences that inhibit splicing.
    Mol Cell Biol. 2000 Sep;20(18):6816-25 PMID: 10958678
  8. An intronic splicing enhancer binds U1 snRNPs to enhance splicing and select 5' splice sites.
    Mol Cell Biol. 2000 Dec;20(24):9225-35 PMID: 11094074
  9. Engineering support vector machine kernels that recognize translation initiation sites.
    Bioinformatics. 2000 Sep;16(9):799-807 PMID: 11108702
  10. Alternative splicing: increasing diversity in the proteomic world.
    Trends Genet. 2001 Feb;17(2):100-7 PMID: 11173120
  11. Evaluation of gene-finding programs on mammalian sequences.
    Genome Res. 2001 May;11(5):817-32 PMID: 11337477
  12. A computational analysis of sequence features involved in recognition of short introns.
    Proc Natl Acad Sci U S A. 2001 Sep 25;98(20):11193-8 PMID: 11572975
  13. Support vector machine prediction of signal peptide cleavage site using a new class of kernels for strings.
    Pac Symp Biocomput. 2002;:649-60 PMID: 11928516
  14. Purification and characterization of native spliceosomes suitable for three-dimensional structural analysis.
    RNA. 2002 Apr;8(4):426-39 PMID: 11991638
  15. Large-scale proteomic analysis of the human spliceosome.
    Genome Res. 2002 Aug;12(8):1231-45 PMID: 12176931
  16. Comprehensive proteomic analysis of the human spliceosome.
    Nature. 2002 Sep 12;419(6903):182-5 PMID: 12226669
  17. Finding signals that regulate alternative splicing in the post-genomic era.
    Genome Biol. 2002 Oct 23;3(11):reviews0008 PMID: 12429065
  18. Distribution and characterization of regulatory elements in the human genome.
    Genome Res. 2002 Dec;12(12):1827-36 PMID: 12466286
  19. Protein composition of human prespliceosomes isolated by a tobramycin affinity-selection method.
    Proc Natl Acad Sci U S A. 2002 Dec 24;99(26):16719-24 PMID: 12477934
  20. Combining hierarchical clustering and self-organizing maps for exploratory analysis of gene expression patterns.
    J Proteome Res. 2002 Sep-Oct;1(5):467-70 PMID: 12645919
  21. A role for exon sequences and splice-site proximity in splice-site selection.
    Cell. 1986 Aug 29;46(5):681-90 PMID: 2427200
  22. RNA splice junctions of different classes of eukaryotes: sequence statistics and functional implications in gene expression.
    Nucleic Acids Res. 1987 Sep 11;15(17):7155-74 PMID: 3658675
  23. Conserved quartets near 5' intron junctions in primate nuclear pre-mRNA.
    J Theor Biol. 1988 Jul 8;133(1):73-84 PMID: 3226142
  24. Exon definition may facilitate splice site selection in RNAs with multiple exons.
    Mol Cell Biol. 1990 Jan;10(1):84-94 PMID: 2136768
  25. Distribution and consensus of branch point signals in eukaryotic genes: a computerized statistical analysis.
    Nucleic Acids Res. 1990 May 25;18(10):3015-9 PMID: 2349097
  26. Human pre-mRNA splicing signals.
    J Theor Biol. 1991 Jun 7;150(3):385-420 PMID: 1798333
  27. Biochemical mechanisms of constitutive and regulated pre-mRNA splicing.
    Annu Rev Cell Biol. 1991;7:559-99 PMID: 1839712
  28. G+C-rich tract in 5' end of human introns.
    J Mol Biol. 1992 Sep 5;227(1):108-13 PMID: 1522582
  29. The mutational spectrum of single base-pair substitutions in mRNA splice junctions of human genes: causes and consequences.
    Hum Genet. 1992 Sep-Oct;90(1-2):41-54 PMID: 1427786
  30. Features of spliceosome evolution and function inferred from an analysis of the information at human splice sites.
    J Mol Biol. 1992 Dec 20;228(4):1124-36 PMID: 1474582
  31. The role of exon sequences in splice site selection.
    Genes Dev. 1993 Mar;7(3):407-18 PMID: 8449402
  32. A mutational analysis of the polypyrimidine tract of introns. Effects of sequence differences in pyrimidine tracts on splicing.
    J Biol Chem. 1993 May 25;268(15):11222-9 PMID: 8496178
  33. Splicing mutants and their second-site suppressors at the dihydrofolate reductase locus in Chinese hamster ovary cells.
    Mol Cell Biol. 1993 Aug;13(8):5085-98 PMID: 8336736
  34. Order of intron removal during splicing of endogenous adenine phosphoribosyltransferase and dihydrofolate reductase pre-mRNA.
    Mol Cell Biol. 1993 Oct;13(10):6211-22 PMID: 8413221
  35. Splicing of Balbiani ring 1 gene pre-mRNA occurs simultaneously with transcription.
    Cell. 1994 Jan 14;76(1):183-92 PMID: 8287477
  36. Exon recognition in vertebrate splicing.
    J Biol Chem. 1995 Feb 10;270(6):2411-4 PMID: 7852296
  37. Distinct binding specificities and functions of higher eukaryotic polypyrimidine tract-binding proteins.
    Science. 1995 May 26;268(5214):1173-6 PMID: 7761834
  38. Selection of novel exon recognition elements from a pool of random sequences.
    Mol Cell Biol. 1995 Nov;15(11):6291-8 PMID: 7565782
  39. An intron splicing enhancer containing a G-rich repeat facilitates inclusion of a vertebrate micro-exon.
    RNA. 1996 Apr;2(4):342-53 PMID: 8634915
  40. Functional analysis of the polypyrimidine tract in pre-mRNA splicing.
    Nucleic Acids Res. 1997 Feb 15;25(4):888-96 PMID: 9016643
  41. Identification of a new class of exonic splicing enhancers by in vivo selection.
    Mol Cell Biol. 1997 Apr;17(4):2143-50 PMID: 9121463
  42. Pyrimidine tracts between the 5' splice site and branch point facilitate splicing and recognition of a small Drosophila intron.
    Mol Cell Biol. 1997 May;17(5):2774-80 PMID: 9111348
  43. Prediction of complete gene structures in human genomic DNA.
    J Mol Biol. 1997 Apr 25;268(1):78-94 PMID: 9149143
  44. G triplets located throughout a class of small vertebrate introns enforce intron borders and regulate splice site selection.
    Mol Cell Biol. 1997 Aug;17(8):4562-71 PMID: 9234714
  45. Functional crosstalk between exon enhancers, polypyrimidine tracts and branchpoint sequences.
    EMBO J. 1997 Dec 1;16(23):7174-83 PMID: 9384594
  46. Statistical features of human exons and their flanking regions.
    Hum Mol Genet. 1998 May;7(5):919-32 PMID: 9536098
  47. Identification of functional exonic splicing enhancer motifs recognized by individual SR proteins.
    Genes Dev. 1998 Jul 1;12(13):1998-2012 PMID: 9649504
  48. Information analysis of human splice site mutations.
    Hum Mutat. 1998;12(3):153-71 PMID: 9711873
  49. Multiple distinct splicing enhancers in the protein-coding sequences of a constitutively spliced pre-mRNA.
    Mol Cell Biol. 1999 Jan;19(1):261-73 PMID: 9858550
  50. Selection and characterization of pre-mRNA splicing enhancers: identification of novel SR protein-specific enhancer sequences.
    Mol Cell Biol. 1999 Mar;19(3):1705-19 PMID: 10022858
  51. Exonic splicing enhancer motif recognized by human SC35 under splicing conditions.
    Mol Cell Biol. 2000 Feb;20(3):1063-71 PMID: 10629063
Article Info
Journal
Genome research
Abbr.
Genome Res
ISSN
1088-9051
DOI
10.1101/gr.1679003
Published
2003-12-00
Pages
2637-50
Language
English
Region
United States
NLM ID
9518021
PMCID
PMC403805
Subset
IM
Grants
NLM NIH HHS · P20 LM007276 · United States
NLM NIH HHS · LM07276-02 · United States
External Links
PubMed source DOI: 10.1101/gr.1679003 PMC Full Text View journal details
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