Protein Modularity of Alternatively Spliced Exons is Associated with Tissue-specific Regulation of Alternative Splicing

Overview

Journal PLoS Genet

Specialty Genetics

Date 2005 Sep 20

PMID 16170410

Citations 32

Authors

Yi Xing

Christopher J Lee

Affiliations

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Abstract

Recent comparative genomic analysis of alternative splicing has shown that protein modularity is an important criterion for functional alternative splicing events. Exons that are alternatively spliced in multiple organisms are much more likely to be an exact multiple of 3 nt in length, representing a class of "modular" exons that can be inserted or removed from the transcripts without affecting the rest of the protein. To understand the precise roles of these modular exons, in this paper we have analyzed microarray data for 3,126 alternatively spliced exons across ten mouse tissues generated by Pan and coworkers. We show that modular exons are strongly associated with tissue-specific regulation of alternative splicing. Exons that are alternatively spliced at uniformly high transcript inclusion levels or uniformly low levels show no preference for protein modularity. In contrast, alternatively spliced exons with dramatic changes of inclusion levels across mouse tissues (referred to as "tissue-switched" exons) are both strikingly biased to be modular and are strongly conserved between human and mouse. The analysis of different subsets of tissue-switched exons shows that the increased protein modularity cannot be explained by the overall exon inclusion level, but is specifically associated with tissue-switched alternative splicing.

Citing Articles

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Inflammation-Induced Alternative Pre-mRNA Splicing in Mouse Alveolar Macrophages.

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The identification of switch-like alternative splicing exons among multiple samples with RNA-Seq data.

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References

Kol G, Lev-Maor G, Ast G . Human-mouse comparative analysis reveals that branch-site plasticity contributes to splicing regulation. Hum Mol Genet. 2005; 14(11):1559-68. DOI: 10.1093/hmg/ddi164. View

Han K, Yeo G, An P, Burge C, Grabowski P . A combinatorial code for splicing silencing: UAGG and GGGG motifs. PLoS Biol. 2005; 3(5):e158. PMC: 1079783. DOI: 10.1371/journal.pbio.0030158. View

Fairbrother W, Yeh R, Sharp P, Burge C . Predictive identification of exonic splicing enhancers in human genes. Science. 2002; 297(5583):1007-13. DOI: 10.1126/science.1073774. View

Xu Q, Modrek B, Lee C . Genome-wide detection of tissue-specific alternative splicing in the human transcriptome. Nucleic Acids Res. 2002; 30(17):3754-66. PMC: 137414. DOI: 10.1093/nar/gkf492. View

Kan Z, States D, Gish W . Selecting for functional alternative splices in ESTs. Genome Res. 2002; 12(12):1837-45. PMC: 187565. DOI: 10.1101/gr.764102. View

Lewis B, Green R, Brenner S . Evidence for the widespread coupling of alternative splicing and nonsense-mediated mRNA decay in humans. Proc Natl Acad Sci U S A. 2002; 100(1):189-92. PMC: 140922. DOI: 10.1073/pnas.0136770100. View

Thanaraj T, Clark F, Muilu J . Conservation of human alternative splice events in mouse. Nucleic Acids Res. 2003; 31(10):2544-52. PMC: 156037. DOI: 10.1093/nar/gkg355. View

Nurtdinov R, Artamonova I, Mironov A, Gelfand M . Low conservation of alternative splicing patterns in the human and mouse genomes. Hum Mol Genet. 2003; 12(11):1313-20. DOI: 10.1093/hmg/ddg137. View

Modrek B, Lee C . Alternative splicing in the human, mouse and rat genomes is associated with an increased frequency of exon creation and/or loss. Nat Genet. 2003; 34(2):177-80. DOI: 10.1038/ng1159. View

10.

Nekrutenko A, Chung W, Li W . ETOPE: Evolutionary test of predicted exons. Nucleic Acids Res. 2003; 31(13):3564-7. PMC: 169003. DOI: 10.1093/nar/gkg597. View

11.

Sorek R, Ast G . Intronic sequences flanking alternatively spliced exons are conserved between human and mouse. Genome Res. 2003; 13(7):1631-7. PMC: 403736. DOI: 10.1101/gr.1208803. View

12.

Boue S, Letunic I, Bork P . Alternative splicing and evolution. Bioessays. 2003; 25(11):1031-4. DOI: 10.1002/bies.10371. View

13.

Garcia J, Gerber S, Sugita S, Sudhof T, Rizo J . A conformational switch in the Piccolo C2A domain regulated by alternative splicing. Nat Struct Mol Biol. 2004; 11(1):45-53. DOI: 10.1038/nsmb707. View

14.

Sorek R, Shamir R, Ast G . How prevalent is functional alternative splicing in the human genome?. Trends Genet. 2004; 20(2):68-71. DOI: 10.1016/j.tig.2003.12.004. View

15.

Hillman R, Green R, Brenner S . An unappreciated role for RNA surveillance. Genome Biol. 2004; 5(2):R8. PMC: 395752. DOI: 10.1186/gb-2004-5-2-r8. View

16.

Resch A, Xing Y, Alekseyenko A, Modrek B, Lee C . Evidence for a subpopulation of conserved alternative splicing events under selection pressure for protein reading frame preservation. Nucleic Acids Res. 2004; 32(4):1261-9. PMC: 390276. DOI: 10.1093/nar/gkh284. View

17.

Itoh H, Washio T, Tomita M . Computational comparative analyses of alternative splicing regulation using full-length cDNA of various eukaryotes. RNA. 2004; 10(7):1005-18. PMC: 1370592. DOI: 10.1261/rna.5221604. View

18.

Sorek R, Shemesh R, Cohen Y, Basechess O, Ast G, Shamir R . A non-EST-based method for exon-skipping prediction. Genome Res. 2004; 14(8):1617-23. PMC: 509271. DOI: 10.1101/gr.2572604. View

19.

Fairbrother W, Holste D, Burge C, Sharp P . Single nucleotide polymorphism-based validation of exonic splicing enhancers. PLoS Biol. 2004; 2(9):E268. PMC: 514884. DOI: 10.1371/journal.pbio.0020268. View

20.

Yeo G, Holste D, Kreiman G, Burge C . Variation in alternative splicing across human tissues. Genome Biol. 2004; 5(10):R74. PMC: 545594. DOI: 10.1186/gb-2004-5-10-r74. View