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Alternative Splicing: a Perspective of the Nematode Model- Caenorhabditis elegans


Affiliations
1 Pittsburgh Institute for Neurodegenerative Diseases, University of Pittsburgh, Pittsburgh, PA 15260, United States
 

The nematode Caenorhabditis elegans is an important, well-studied organism used in biomedical research as a model for human development, genetics, ageing, and disease. This paper reviews some basic information, recent progress and future challenges for functional genomics and bioinformatics in the area of alternative splicing. It also highlights the unique methodology adopted by us to study and to detect novel alternatively spliced transcripst from C. elegans genome.

Keywords

Alternative Splicing, Caenorhabditis elegans, Gene/exon Prediction, Genome Analysis
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  • Agrawal R and Stormo GD (2006) Using mRNAs lengths to accurately predict the alternatively spliced gene products in Caenorhabditis elegans. Bioinformatics. 22, 1239-1244.
  • Alekseyenko AV, Kim N and Lee CJ ( 2007) Global analysis of exon creation versus loss and the role of alternative splicing in 17 vertebrate genomes.RNA. 13, 661-670.
  • Bingham JL, Carrigan PE, Miller LJ, Srinivasan S.(2008) Extent and diversity of human alternative splicing established by complementary database annotation and microarray analysis. OMICS. 12, 83-92.
  • Black DL (2003) Mechanisms of alternative pre-messenger RNA splicing. Annu. Rev. Biochem. 72, 291–336.
  • Bonizzoni P, Rizzi R and Pesole G (2006) Computational methods for alternative splicing prediction. Brief Funct. Genomic Proteomic. 5, 46-51.
  • Brett D, Hanke J, Lehmann G, Haase S, Delbrück S, Krueger S, Reich J, Bork P (2000) EST comparison indicates 38% of human mRNAs contain possible alternative splice forms. FEBS Lett. 474, 83-86.
  • Brett D, Pospisil H, Valcarcel J, Reich J and Bork P (2002) Alternative splicing and genome complexity. Nature Genet. 30, 29–30.
  • Cawley S and Pachter L (2003) HMM sampling and applications to gene finding and AS. Bioinformatics. 19, 36–41.
  • Chen CD, Kobayashi R and Helfman DM (1999) Binding of hnRNP H to an exonic splicing silencer is involved in the regulation of alternative splicing of the rat beta-tropomyosin gene. Genes Dev. 13, 593–606.
  • Christopher L and Qi W (2005) Bioinformatics analysis of alternative splicing. Briefings in Bioinformatics. 6(1), 23-33.
  • Claverie JM (2001) Gene number. What if there are only 30,000 human genes? Science. 291, 1255–1257.
  • Croft L, Schandorff S, Clark F, Burrage K, Arctander P, and Mattick JS (2000) ISIS, the intron information system, reveals the high frequency of alternative splicing in the human genome. Nat. Genet. 24, 340–341.
  • Culetto E and Sattelle DB (2000) A role for Caenorhabditis elegans in understanding the function and interactions of human disease genes. Human Molecular Genetics. 9, 869- 877.
  • Dror G, Soreck R and Shamir R (2005) Accurate identification of alternatively spliced exons using support vector machine. Bioinformatics. 21, 897–901.
  • Florea L (2006) Bioinformatics of alternative splicing and its regulation. Brief Bioinform. 7, 55-69.
  • Grabowski PJ (1998) Splicing regulation in neurons: tinkering with cell-specific control. Cell. 92, 709-712.
  • Graveley BR (2001) Alternative splicing: Increasing diversity in the proteomic world. Trends Genet. 17, 100-107.
  • Guo HA, Lutsch JK, Leheste G, et al., (2001) A: Two splice variants of the Wilms’ tumor 1 gene have distinct functions during sex determination and nephron formation. Cell. 106, 319-329.
  • Gupta S, Zink D, Korn B, Vingron M and Haas SA (2004) Genome wide identification and classification of alternative splicing based on EST data. Bioinformatics. 20 (16), 2579-2585.
  • Hagiwara M (2005) Alternative splicing: a new drug target of the post-genome era Biochim. Biophys. Acta., 1754, 324–331.
  • Hammes A, Guo JK, Lutsch G, Leheste JR, Landrock D, Ziegler U, Gubler MC and Schedl A (2001) Two splice variants of the Wilms’ tumor 1 gene have distinct functions during sex determination and nephron formation. Cell .106, 319–329.
  • Harrington ED, Buoe S, Valcarcel J, Reich JG, Bork P (2004) Estimating rates of alternative splicing in mammals and invertebrates. Nat Genet. 36, 916–917.
  • Herrlich P, Zoller M, Ponta H (1993) CD44 splice variants: Metastases meets lymphocytes. Immunol Today 14,395–399,
  • Inoue K, Hoshijima K, Sakamoto H, Shimura Y (1990) Binding of the Drosophila sex-lethal gene product to the alternative splice site of transformer primary transcript. Nature. 29, 344,461–463.
  • International Human Genome Sequencing Consortium (2001) Initial sequencing and analysis of the human genome. Nature. 409, 860-921.
  • Jiang ZH and Wu JY (1999) Alternative splicing and programmed cell death. Proc. Soc. Exp. Biol. Med. 220, 64–72.
  • Johnson JM, Castle J, Garrett-Engele P, Kan Z, Loerch PM, Armour CD, Santos R, Schadt EE, Stoughton R and Shoemaker DD (2003) Genome-wide survey of human alternative premRNA splicing with exon junction microarrays.Science. 302, 2141-2144.
  • Joseph R, Dou D and Tsang W (1995) Neuronatin mRNA: alternatively spliced forms of a novel brain-specific mammalian developmental gene. Brain Res. 690, 92–98.
  • Kan Z, Rouchka EC, Gish WR and States DJ (2001) Gene structure prediction and alternative splicing analysis using genomically aligned ESTs. Genome Res. 11, 889–900.
  • Kan Z, Startes D and Gish W (2002) Selecting for functional alternative splices in ESTs. Genome Res. 12, 1837–1845.
  • Karpova AY, Ronco LV and Howley PM (2001) Functional characterization of interferon regulatory factor 3a (IRF-3a), an alternative splice isoform of IRF-3. Mol. Cell. Biol. 21, 4169–4176.
  • Kashyap L and Tabish M (2007c) Alternatively spliced isoforms encoded by cadherin genes from C. elegans genome. Bioinformation. 2, 50-56.
  • Kashyap L, Tabish M, Ganesh S et al., (2007a) Computational and molecular characterization of multiple isoforms of lfe-2 gene in nematode C. Elegans. Bioinformation. 2, 17-21.
  • Kashyap L, Tabish M, Ganesh S et al., (2007b) Identification and comparative analysis of novel alternatively spliced transcripts of RhoGEF domain encoding gene in C. elegans and C. briggsae, Bioinformation. 2, 43-49.
  • Kim E, Magen A, Ast G (2007) Different levels of alternative splicing among eukaryotes. Nucleic Acids Res. 35, 125-131.
  • Kim H, Klein R, Majewski J and Ott J (2004) Estimating rates of alternative splicing in mammals and invertebrates. Nat. Genet. 36, 915–916.
  • Kochiwa H, Suzuki R, Washio T, Saito R, Bono H, Carninci P, Okazaki Y, Miki R, Hayashizaki Y, and Tomita M (2002) Inferring alternative splicing patterns in mouse from a full-length cDNA library and microarray data. Genome Res. 12, 1286–1293.
  • Leipzig J, Pevzner P and Heber S (2004) The Alternative Splicing Gallery (ASG): bridging the gap between genome and transcriptome. Nucleic Acids Res. 32, 3977-3983.
  • Leparc GG and Mitra RD (2007) Non-ESTbased prediction of novel alternatively spliced cassette exons with cell signaling function in Caenorhabditis elegans and human. Nucleic Acids Res. 35, 3192-3202.
  • Liu W, Qian C and Francke U (1997) Silent mutation induces exon skipping of fibrillin-1 gene in Marfan syndrome. Nature Genet. 16, 328–329.
  • Lopez AJ (1998) Alternative splicing of premRNA: developmental consequences and mechanisms of regulation. Annu. Rev. Genet. 32, 279-305.
  • Matlin AJ, Clark F and Smith CWJ (2005) Understanding alternative splicing: towards a cellular code. Nat Rev Mol Cell Biol. 6, 386– 398.
  • Mironov AA, Fickett JW and Gelfand MS (1999).Frequent alternative splicing of human genes Genome Res. 9, 1288–1293.
  • Modrek B and Lee CJ (2003) Alternative splicing in the human, mouse and rat genomes is associated with an increased frequency of exon creation and/or loss. Nat. Genet. 34, 177– 180.
  • Modrek B, Resch A, Grasso C and Lee C (2001) Genome-wide analysis of alternative splicing using human expressed sequence data. Nucleic Acids Res. 29, 2850-2859.
  • Ohler U, Shomron N, Burge CB ( 2005) Recognition of unknown conserved alternatively spliced exons. PLoS Comput. Biol. 1(2), e15.
  • Pajares MJ, Ezponda T, Catena R, Calvo A, Pio R and Montuenga LM (2007) Alternative splicing: an emerging topic in molecular and clinical oncology. The lancet Oncology. 8, 349- 357.
  • Philipps DL, Park JW, Graveley BR (2004) A computational and experimental approach toward a priori identification of alternatively spliced exons. RNA 10(12), 1838–1844.
  • Ratsch G, Sonnenburg S, Scholkopf B (2005) RASE: recognition of alternatively spliced exons in C.elegans. Bioinformatics. 21 (1), i369–i377.
  • Sanford JR and Caceres F (2004) Pre-mRNA splicing: life at the centre of the central dogma. J. Cell Sci. 117(26), 6261- 6263.
  • Schmucker D, Clemens JC, Shu H, Worby CA, Xiao J, Muda M, Dixon JE and Zipursky SL (2000) Drosophila Dscam is an axon guidance receptor exhibiting extraordinary molecular diversity. Cell .101, 671-684.
  • Sharp PA (1994) Split genes and RNA splicing. Cell. 77, 805–815.
  • Singh RN (2007) Unfolding the mystery of alternative splicing through a unique method of in vivo selection. Frontiers in Bioscience. 12, 3263-3272.
  • Smith CW and Valcarcel J (2000) Alternative pre-mRNA splicing: the logic of. combinatorial
  • control. Trend Biochem. Sci. 25, 381-388. 55. Sorek R, Shamir R and Ast G (2004) How prevalent is functional alternative splicing in the human genome? Trends Genet. 20, 68–71.
  • Sosnowski BA, Belote JM and McKeown M (1989) Sex-specific alternative splicing of RNA from the transformer gene results from sequence-dependent splice site blockage. Cell. 58, 449-459.
  • Srinivasan K, Shiue L, Hayes JD, Centers R, Fitzwater S, Loewen R, Edmondson LR, Bryant J, Smith M, Rommelfanger C, Welch V, Clark TA, Sugnet CW, Howe KJ, Mandel- Gutfreund Y and Ares M Jr (2005) Detection and measurement of alternative splicing using splicing-sensitive microarrays. Methods. 37, 345-59.
  • Stallings-Mann ML, Ludwiczak RL, Klinger KW, Rottman F (1996) Alternative splicing of exon 3 of the human growth hormone receptor is the result of an unusual genetic polymorphism. Proc. Natl. Acad. Sci. USA. 93, 12394–12399.
  • Sternberg PW (2001) Working in the postgenomic C. elegans world. Cell. 105, 173–176.
  • Stetefeld J and Ruegg MA (2005) Structural and functional diversity generated by alternative mRNA splicing. Trends Biochem. Sci. 30, 515–521.
  • Sylvain F and Thomas S (2005) Integrating alternative splicing detection into gene prediction. BMC Bioinformatics. 6, 25.
  • Tabish M and Ticku MK (2004) Alternate splice transcripts of mouse NR2B gene. Neurochem. Int. 44, 339-343.
  • Tabish M, Clegg RA, Rees HH and Fisher MJ (1999) Organization and alternative splicing of the Caenorhabditis elegans cAMP-dependent protein kinase catalytic-subunit gene (kin-1). Biochem. J. 339, 209-216.
  • Talavera D, Hospital A, Orozco M and de la Cruz X (2007) A procedure for the identification of homologous alternative splicing events. BMC Bioinformatics.8(1),260.
  • Venter JC, Adams MD, Myers EW, Li PW, Mural RJ, Sutton GG, Smith HO, Yandell M, Evans CA, Holt RA, et al. (2001) The sequence of the human genome. Science. 291, 1304- 1351.
  • Wilson CA, Payton MN, Elliott GS, Buaas FW, Cajulis EE, Grosshans D, Ramos L, Reese DM, Slamon DJ and Calzone FJ (1997) Differential sub-cellular localization, expression and biological toxicity of BRCA1 and the splice variant BRCA1-D11b. Oncogene. 14, 1-16.

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  • Alternative Splicing: a Perspective of the Nematode Model- Caenorhabditis elegans

Abstract Views: 472  |  PDF Views: 76

Authors

Luv Kashyap
Pittsburgh Institute for Neurodegenerative Diseases, University of Pittsburgh, Pittsburgh, PA 15260, United States

Abstract


The nematode Caenorhabditis elegans is an important, well-studied organism used in biomedical research as a model for human development, genetics, ageing, and disease. This paper reviews some basic information, recent progress and future challenges for functional genomics and bioinformatics in the area of alternative splicing. It also highlights the unique methodology adopted by us to study and to detect novel alternatively spliced transcripst from C. elegans genome.

Keywords


Alternative Splicing, Caenorhabditis elegans, Gene/exon Prediction, Genome Analysis

References





DOI: https://doi.org/10.17485/ijst%2F2008%2Fv1i6%2F29590