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MeSH Review

Alternative Splicing

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Disease relevance of Alternative Splicing


Psychiatry related information on Alternative Splicing


High impact information on Alternative Splicing

  • Recent work has focused on regulation of CD45 expression and alternative splicing, isoform-specific differences in signal transduction, and regulation of phosphatase activity [10].
  • The single calpastatin gene can produce eight or more calpastatin polypeptides ranging from 17 to 85 kDa by use of different promoters and alternative splicing events [11].
  • The D2 and D3 receptors vary in certain tissues and species as a result of alternative splicing, and the human D4 receptor gene exhibits extensive polymorphic variation [12].
  • Alternative splicing of Dscam generates an enormous molecular diversity with maximally 38,016 different receptors [13].
  • Genome-wide quantitative analysis of alternative splicing using a custom Affymetrix microarray indicate that the neuronal splicing factor Nova2 regulates a biologically coherent set of transcripts encoding synaptic proteins [14].
  • Nova1 and Nova2 regulate alternative splicing of ~700 brain transcripts by directly binding to clusters of YCAY elements. [15]
  • The position at which the Nova1 and Nova2 proteins bind a pre-mRNA dictate the outcome of alternative splice site selection. [16]

Chemical compound and disease context of Alternative Splicing


Biological context of Alternative Splicing


Anatomical context of Alternative Splicing


Associations of Alternative Splicing with chemical compounds


Gene context of Alternative Splicing


Analytical, diagnostic and therapeutic context of Alternative Splicing


  1. A slow RNA polymerase II affects alternative splicing in vivo. de la Mata, M., Alonso, C.R., Kadener, S., Fededa, J.P., Blaustein, M., Pelisch, F., Cramer, P., Bentley, D., Kornblihtt, A.R. Mol. Cell (2003) [Pubmed]
  2. Loss of the muscle-specific chloride channel in type 1 myotonic dystrophy due to misregulated alternative splicing. Charlet-B, N., Savkur, R.S., Singh, G., Philips, A.V., Grice, E.A., Cooper, T.A. Mol. Cell (2002) [Pubmed]
  3. Cell-specific regulation of agrin RNA splicing in the chick ciliary ganglion. Smith, M.A., O'Dowd, D.K. Neuron (1994) [Pubmed]
  4. Up-regulation of specific tyrosinase mRNAs in mouse melanomas with the c2j gene substituted for the wild-type tyrosinase allele: utilization in design of syngeneic immunotherapy models. Le Fur, N., Silvers, W.K., Kelsall, S.R., Mintz, B. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  5. Interleukin (IL) 15/IL-T production by the adult T-cell leukemia cell line HuT-102 is associated with a human T-cell lymphotrophic virus type I region /IL-15 fusion message that lacks many upstream AUGs that normally attenuates IL-15 mRNA translation. Bamford, R.N., Battiata, A.P., Burton, J.D., Sharma, H., Waldmann, T.A. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  6. Levels and alternative splicing of amyloid beta protein precursor (APP) transcripts in brains of APP transgenic mice and humans with Alzheimer's disease. Rockenstein, E.M., McConlogue, L., Tan, H., Power, M., Masliah, E., Mucke, L. J. Biol. Chem. (1995) [Pubmed]
  7. MyoD is indispensable for muscle-specific alternative splicing in mouse mitochondrial ATP synthase gamma-subunit pre-mRNA. Ichida, M., Endo, H., Ikeda, U., Matsuda, C., Ueno, E., Shimada, K., Kagawa, Y. J. Biol. Chem. (1998) [Pubmed]
  8. Growth factors and muscle ageing. Goldspink, G., Harridge, S.D. Exp. Gerontol. (2004) [Pubmed]
  9. Rett syndrome: clinical and molecular update. Percy, A.K., Lane, J.B. Curr. Opin. Pediatr. (2004) [Pubmed]
  10. CD45: a critical regulator of signaling thresholds in immune cells. Hermiston, M.L., Xu, Z., Weiss, A. Annu. Rev. Immunol. (2003) [Pubmed]
  11. The calpain system. Goll, D.E., Thompson, V.F., Li, H., Wei, W., Cong, J. Physiol. Rev. (2003) [Pubmed]
  12. Dopamine receptors: from structure to function. Missale, C., Nash, S.R., Robinson, S.W., Jaber, M., Caron, M.G. Physiol. Rev. (1998) [Pubmed]
  13. The molecular diversity of dscam is functionally required for neuronal wiring specificity in Drosophila. Chen, B.E., Kondo, M., Garnier, A., Watson, F.L., Püettmann-Holgado, R., Lamar, D.R., Schmucker, D. Cell (2006) [Pubmed]
  14. Nova regulates brain-specific splicing to shape the synapse. Ule, J., Ule, A., Spencer, J., Williams, A., Hu, J.S., Cline, M., Wang, H., Clark, T., Fraser, C., Ruggiu, M., Zeeberg, B.R., Kane, D., Weinstein, J.N., Blume, J., Darnell, R.B. Nat. Genet. (2005) [Pubmed]
  15. Integrative modeling defines the Nova splicing-regulatory network and its combinatorial controls. Zhang, C., Frias, M.A., Mele, A., Ruggiu, M., Eom, T., Marney, C.B., Wang, H., Licatalosi, D.D., Fak, J.J., Darnell, R.B. Science. (2010) [Pubmed]
  16. HITS-CLIP yields genome-wide insights into brain alternative RNA processing. Licatalosi, D.D., Mele, A., Fak, J.J., Ule, J., Kayikci, M., Chi, S.W., Clark, T.A., Schweitzer, A.C., Blume, J.E., Wang, X., Darnell, J.C., Darnell, R.B. Nature. (2008) [Pubmed]
  17. Glanzmann's thrombasthenia associated with deletion-insertion and alternative splicing in the glycoprotein IIb gene. Peretz, H., Rosenberg, N., Usher, S., Graff, E., Newman, P.J., Coller, B.S., Seligsohn, U. Blood (1995) [Pubmed]
  18. De novo ceramide regulates the alternative splicing of caspase 9 and Bcl-x in A549 lung adenocarcinoma cells. Dependence on protein phosphatase-1. Chalfant, C.E., Rathman, K., Pinkerman, R.L., Wood, R.E., Obeid, L.M., Ogretmen, B., Hannun, Y.A. J. Biol. Chem. (2002) [Pubmed]
  19. Pancreatic islets and insulinoma cells express a novel isoform of group VIA phospholipase A2 (iPLA2 beta) that participates in glucose-stimulated insulin secretion and is not produced by alternate splicing of the iPLA2 beta transcript. Ramanadham, S., Song, H., Hsu, F.F., Zhang, S., Crankshaw, M., Grant, G.A., Newgard, C.B., Bao, S., Ma, Z., Turk, J. Biochemistry (2003) [Pubmed]
  20. Complete genomic structure of the human nebulin gene and identification of alternatively spliced transcripts. Donner, K., Sandbacka, M., Lehtokari, V.L., Wallgren-Pettersson, C., Pelin, K. Eur. J. Hum. Genet. (2004) [Pubmed]
  21. The human peripheral benzodiazepine receptor gene: cloning and characterization of alternative splicing in normal tissues and in a patient with congenital lipoid adrenal hyperplasia. Lin, D., Chang, Y.J., Strauss, J.F., Miller, W.L. Genomics (1993) [Pubmed]
  22. Mutually exclusive splicing of the insect Dscam pre-mRNA directed by competing intronic RNA secondary structures. Graveley, B.R. Cell (2005) [Pubmed]
  23. Alternative splicing regulation impacts heart development. Cooper, T.A. Cell (2005) [Pubmed]
  24. Human and murine FMR-1: alternative splicing and translational initiation downstream of the CGG-repeat. Ashley, C.T., Sutcliffe, J.S., Kunst, C.B., Leiner, H.A., Eichler, E.E., Nelson, D.L., Warren, S.T. Nat. Genet. (1993) [Pubmed]
  25. Aberrant regulation of insulin receptor alternative splicing is associated with insulin resistance in myotonic dystrophy. Savkur, R.S., Philips, A.V., Cooper, T.A. Nat. Genet. (2001) [Pubmed]
  26. The bcl-2 gene encodes a novel G protein. Haldar, S., Beatty, C., Tsujimoto, Y., Croce, C.M. Nature (1989) [Pubmed]
  27. Nova2 regulates neuronal migration through an RNA switch in disabled-1 signaling. Yano, M., Hayakawa-Yano, Y., Mele, A., Darnell, R.B. Neuron. (2010) [Pubmed]
  28. Nova-1 regulates neuron-specific alternative splicing and is essential for neuronal viability. Jensen, K.B., Dredge, B.K., Stefani, G., Zhong, R., Buckanovich, R.J., Okano, H.J., Yang, Y.Y., Darnell, R.B. Neuron. (2000) [Pubmed]
  29. Alternative splicing accounts for the four forms of myelin basic protein. de Ferra, F., Engh, H., Hudson, L., Kamholz, J., Puckett, C., Molineaux, S., Lazzarini, R.A. Cell (1985) [Pubmed]
  30. ASF/SF2-regulated CaMKIIdelta alternative splicing temporally reprograms excitation-contraction coupling in cardiac muscle. Xu, X., Yang, D., Ding, J.H., Wang, W., Chu, P.H., Dalton, N.D., Wang, H.Y., Bermingham, J.R., Ye, Z., Liu, F., Rosenfeld, M.G., Manley, J.L., Ross, J., Chen, J., Xiao, R.P., Cheng, H., Fu, X.D. Cell (2005) [Pubmed]
  31. Alternative splicing of the sex determination gene transformer-2 is sex-specific in the germ line but not in the soma. Mattox, W., Palmer, M.J., Baker, B.S. Genes Dev. (1990) [Pubmed]
  32. Negative regulation of CD45 by differential homodimerization of the alternatively spliced isoforms. Xu, Z., Weiss, A. Nat. Immunol. (2002) [Pubmed]
  33. Normal B lymphocyte development but impaired T cell maturation in CD45-exon6 protein tyrosine phosphatase-deficient mice. Kishihara, K., Penninger, J., Wallace, V.A., Kündig, T.M., Kawai, K., Wakeham, A., Timms, E., Pfeffer, K., Ohashi, P.S., Thomas, M.L. Cell (1993) [Pubmed]
  34. Developmentally regulated alternative splicing of Drosophila integrin PS2 alpha transcripts. Brown, N.H., King, D.L., Wilcox, M., Kafatos, F.C. Cell (1989) [Pubmed]
  35. Novel activin receptors: distinct genes and alternative mRNA splicing generate a repertoire of serine/threonine kinase receptors. Attisano, L., Wrana, J.L., Cheifetz, S., Massagué, J. Cell (1992) [Pubmed]
  36. Alternative splicing directs the expression of two D2 dopamine receptor isoforms. Giros, B., Sokoloff, P., Martres, M.P., Riou, J.F., Emorine, L.J., Schwartz, J.C. Nature (1989) [Pubmed]
  37. Alternative splicing of C-terminal tail of prostaglandin E receptor subtype EP3 determines G-protein specificity. Namba, T., Sugimoto, Y., Negishi, M., Irie, A., Ushikubi, F., Kakizuka, A., Ito, S., Ichikawa, A., Narumiya, S. Nature (1993) [Pubmed]
  38. Crystal structures of two FGF-FGFR complexes reveal the determinants of ligand-receptor specificity. Plotnikov, A.N., Hubbard, S.R., Schlessinger, J., Mohammadi, M. Cell (2000) [Pubmed]
  39. The role of specific protein-RNA and protein-protein interactions in positive and negative control of pre-mRNA splicing by Transformer 2. Amrein, H., Hedley, M.L., Maniatis, T. Cell (1994) [Pubmed]
  40. Alternative splicing of Drosophila Dscam generates axon guidance receptors that exhibit isoform-specific homophilic binding. Wojtowicz, W.M., Flanagan, J.J., Millard, S.S., Zipursky, S.L., Clemens, J.C. Cell (2004) [Pubmed]
  41. Molecular analysis of the para locus, a sodium channel gene in Drosophila. Loughney, K., Kreber, R., Ganetzky, B. Cell (1989) [Pubmed]
  42. Neurofibromatosis 2 tumour suppressor schwannomin interacts with betaII-spectrin. Scoles, D.R., Huynh, D.P., Morcos, P.A., Coulsell, E.R., Robinson, N.G., Tamanoi, F., Pulst, S.M. Nat. Genet. (1998) [Pubmed]
  43. Neuroligin 1: a splice site-specific ligand for beta-neurexins. Ichtchenko, K., Hata, Y., Nguyen, T., Ullrich, B., Missler, M., Moomaw, C., Südhof, T.C. Cell (1995) [Pubmed]
  44. A specific ovarian tumor protein isoform is required for efficient differentiation of germ cells in Drosophila oogenesis. Steinhauer, W.R., Kalfayan, L.J. Genes Dev. (1992) [Pubmed]
  45. Alternative splicing of human glucose-6-phosphate dehydrogenase messenger RNA in different tissues. Hirono, A., Beutler, E. J. Clin. Invest. (1989) [Pubmed]
  46. Developmental and functional impairment of T cells in mice lacking CD3 zeta chains. Ohno, H., Aoe, T., Taki, S., Kitamura, D., Ishida, Y., Rajewsky, K., Saito, T. EMBO J. (1993) [Pubmed]
  47. Molecular cloning and functional expression of two monocyte chemoattractant protein 1 receptors reveals alternative splicing of the carboxyl-terminal tails. Charo, I.F., Myers, S.J., Herman, A., Franci, C., Connolly, A.J., Coughlin, S.R. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
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