Table of Contents Author Guidelines Submit a Manuscript
International Journal of Cell Biology
Volume 2013, Article ID 810572, 16 pages
http://dx.doi.org/10.1155/2013/810572
Review Article

Role of Pseudoexons and Pseudointrons in Human Cancer

1Department of Life Sciences, University of Trieste, Via A. Valerio 28, 34127 Trieste, Italy
2International Centre for Genetic Engineering and Biotechnology (ICGEB), 34149 Trieste, Italy
3Human Development and Health, University of Southampton, Duthie Building, Mailpoint 808, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK
4Human Genetics Division, University of Southampton, Duthie Building, Mailpoint 808, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK

Received 17 June 2013; Accepted 9 August 2013

Academic Editor: Claudia Ghigna

Copyright © 2013 Maurizio Romano et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. L. T. Chow, R. E. Gelinas, T. R. Broker, and R. J. Roberts, “An amazing sequence arrangement at the 5′ ends of adenovirus 2 messenger RNA,” Cell, vol. 12, no. 1, pp. 1–8, 1977. View at Google Scholar · View at Scopus
  2. S. M. Berget, C. Moore, and P. A. Sharp, “Spliced segments at the 5′ terminus of adenovirus 2 late mRNA,” Proceedings of the National Academy of Sciences of the United States of America, vol. 74, no. 8, pp. 3171–3175, 1977. View at Google Scholar · View at Scopus
  3. J. E. Darnell Jr., “Reflections on the history of pre-mRNA processing and highlights of current knowledge: a unified picture,” RNA, vol. 19, no. 4, pp. 443–460, 2013. View at Publisher · View at Google Scholar
  4. T. W. Nilsen, “The spliceosome: the most complex macromolecular machine in the cell?” Bioessays, vol. 25, no. 12, pp. 1147–1149, 2003. View at Publisher · View at Google Scholar · View at Scopus
  5. C. L. Will and R. Lührmann, “Spliceosome structure and function,” Cold Spring Harbor Perspectives in Biology, vol. 3, no. 7, 2011. View at Google Scholar · View at Scopus
  6. D. R. Semlow and J. P. Staley, “Staying on message: ensuring fidelity in pre-mRNA splicing,” Trends in Biochemical Sciences, vol. 37, no. 7, pp. 263–273, 2012. View at Publisher · View at Google Scholar · View at Scopus
  7. L. Cartegni, S. L. Chew, and A. R. Krainer, “Listening to silence and understanding nonsense: exonic mutations that affect splicing,” Nature Reviews Genetics, vol. 3, no. 4, pp. 285–298, 2002. View at Publisher · View at Google Scholar · View at Scopus
  8. K. J. Hertel, “Combinatorial control of exon recognition,” The Journal of Biological Chemistry, vol. 283, no. 3, pp. 1211–1215, 2008. View at Publisher · View at Google Scholar · View at Scopus
  9. A. R. Kornblihtt, I. E. Schor, M. Allo, G. Dujardin, E. Petrillo, and M. J. Munoz, “Alternative splicing: a pivotal step between eukaryotic transcription and translation,” Nature Reviews Molecular Cell Biology, vol. 14, pp. 153–165, 2013. View at Google Scholar
  10. B. Chabot, “Directing alternative splicing: cast and scenarios,” Trends in Genetics, vol. 12, no. 11, pp. 472–478, 1996. View at Publisher · View at Google Scholar · View at Scopus
  11. D. L. Black, “Mechanisms of alternative pre-messenger RNA splicing,” Annual Review of Biochemistry, vol. 72, pp. 291–336, 2003. View at Publisher · View at Google Scholar · View at Scopus
  12. Y. Wang, X. Xiao, J. Zhang et al., “A complex network of factors with overlapping affinities represses splicing through intronic elements,” Nature Structural & Molecular Biology, vol. 20, pp. 36–45, 2013. View at Google Scholar
  13. S. C. Huelga, A. Q. Vu, J. D. Arnold et al., “Integrative genome-wide analysis reveals cooperative regulation of alternative splicing by hnRNP proteins,” Cell Reports, vol. 1, no. 2, pp. 167–178, 2012. View at Google Scholar
  14. S. Pandit, Y. Zhou, L. Shiue et al., “Genome-wide analysis reveals SR protein cooperation and competition in regulated splicing,” Molecular Cell, vol. 50, pp. 223–235, 2013. View at Google Scholar
  15. T. D. Schaal and T. Maniatis, “Multiple distinct splicing enhancers in the protein-coding sequences of a constitutively spliced pre-mRNA,” Molecular and Cellular Biology, vol. 19, no. 1, pp. 261–273, 1999. View at Google Scholar · View at Scopus
  16. B. R. Graveley, “Sorting out the complexity of SR protein functions,” RNA, vol. 6, no. 9, pp. 1197–1211, 2000. View at Publisher · View at Google Scholar · View at Scopus
  17. R. Martinez-Contreras, P. Cloutier, L. Shkreta, J. F. Fisette, T. Revil, and B. Chabot, “hnRNP proteins and splicing control,” Advances in Experimental Medicine and Biology, vol. 623, pp. 123–147, 2007. View at Google Scholar · View at Scopus
  18. J. Hnilicová and D. Staněk, “Where splicing joins chromatin,” Nucleus, vol. 2, no. 3, pp. 182–188, 2011. View at Publisher · View at Google Scholar · View at Scopus
  19. L. I. G. Acuña, A. Fiszbein, M. Alló, I. E. Schor, and A. R. Kornblihtt, “Connections between chromatin signatures and splicing,” Wiley Interdisciplinary Reviews, vol. 4, no. 1, pp. 77–91, 2013. View at Publisher · View at Google Scholar
  20. G. Dujardin, C. Lafaille, E. Petrillo et al., “Transcriptional elongation and alternative splicing,” Biochimica et Biophysica Acta, vol. 1829, no. 1, pp. 134–140, 2013. View at Publisher · View at Google Scholar
  21. E. Buratti and F. E. Baralle, “Influence of RNA secondary structure on the pre-mRNA splicing process,” Molecular and Cellular Biology, vol. 24, no. 24, pp. 10505–10514, 2004. View at Publisher · View at Google Scholar · View at Scopus
  22. A. Khanna and S. Stamm, “Regulation of alternative splicing by short non-coding nuclear RNAs,” RNA Biology, vol. 7, no. 4, pp. 480–485, 2010. View at Publisher · View at Google Scholar · View at Scopus
  23. R. F. Luco and T. Misteli, “More than a splicing code: integrating the role of RNA, chromatin and non-coding RNA in alternative splicing regulation,” Current Opinion in Genetics and Development, vol. 21, no. 4, pp. 366–372, 2011. View at Publisher · View at Google Scholar · View at Scopus
  24. G. Biamonti and J. F. Caceres, “Cellular stress and RNA splicing,” Trends in Biochemical Sciences, vol. 34, no. 3, pp. 146–153, 2009. View at Publisher · View at Google Scholar · View at Scopus
  25. O. Kelemen, P. Convertini, Z. Zhang et al., “Function of alternative splicing,” Gene, vol. 514, pp. 1–30, 2013. View at Google Scholar
  26. T. L. Johnson and J. Vilardell, “Regulated pre-mRNA splicing: the ghostwriter of the eukaryotic genome,” Biochimica et Biophysica Acta, vol. 1819, no. 6, pp. 538–545, 2012. View at Publisher · View at Google Scholar · View at Scopus
  27. S. Zheng and D. L. Black, “Alternative pre-mRNA splicing in neurons: growing up and extending its reach,” Trends in Genetics, vol. 29, no. 8, pp. 442–448, 2013. View at Publisher · View at Google Scholar
  28. A. D. Norris and J. A. Calarco, “Emerging roles of alternative pre-mRNA splicing regulation in neuronal development and function,” Frontiers in Neuroscience, vol. 6, no. 122, 2012. View at Publisher · View at Google Scholar
  29. J. S. Mattick, “The central role of RNA in human development and cognition,” FEBS Letters, vol. 585, no. 11, pp. 1600–1616, 2011. View at Publisher · View at Google Scholar · View at Scopus
  30. P. Grabowski, “Alternative splicing takes shape during neuronal development,” Current Opinion in Genetics and Development, vol. 21, no. 4, pp. 388–394, 2011. View at Publisher · View at Google Scholar · View at Scopus
  31. K. Yap and E. V. Makeyev, “Regulation of gene expression in mammalian nervous system through alternative pre-mRNA splicing coupled with RNA quality control mechanisms,” Molecular and Cellular Neuroscience, 2013. View at Publisher · View at Google Scholar
  32. A. Montecucco and G. Biamonti, “Pre-mRNA processing factors meet the DNA damage response,” Frontiers in Genetics, vol. 4, no. 102, 2013. View at Google Scholar
  33. Z. Melamed, A. Levy, R. Ashwal-Fluss et al., “Alternative splicing regulates biogenesis of miRNAs located across exon-intron junctions,” Molecular Cell, vol. 50, no. 6, pp. 869–881, 2013. View at Publisher · View at Google Scholar
  34. N. Skoko, M. Baralle, S. Tisminetzky, and E. Buratti, “InTRONs in biotech,” Molecular Biotechnology, vol. 48, no. 3, pp. 290–297, 2011. View at Publisher · View at Google Scholar · View at Scopus
  35. Q. Pan, O. Shai, L. J. Lee, B. J. Frey, and B. J. Blencowe, “Deep surveying of alternative splicing complexity in the human transcriptome by high-throughput sequencing,” Nature Genetics, vol. 40, pp. 1413–1415, 2008. View at Publisher · View at Google Scholar
  36. E. Buratti, M. Baralle, and F. E. Baralle, “Defective splicing, disease and therapy: searching for master checkpoints in exon definition,” Nucleic Acids Research, vol. 34, no. 12, pp. 3494–3510, 2006. View at Publisher · View at Google Scholar · View at Scopus
  37. M. Krawczak, N. S. T. Thomas, B. Hundrieser et al., “Single base-pair substitutions in exon-intron junctions of human genes: nature, distribution, and consequences for mRNA splicing,” Human Mutation, vol. 28, no. 2, pp. 150–158, 2007. View at Publisher · View at Google Scholar · View at Scopus
  38. A. Dhir and E. Buratti, “Alternative splicing: role of pseudoexons in human disease and potential therapeutic strategies: minireview,” FEBS Journal, vol. 277, no. 4, pp. 841–855, 2010. View at Publisher · View at Google Scholar · View at Scopus
  39. D. Baralle, A. Lucassen, and E. Buratti, “Missed threads: the impact of pre-mRNA splicing defects on clinical practice,” EMBO Reports, vol. 10, no. 8, pp. 810–816, 2009. View at Publisher · View at Google Scholar · View at Scopus
  40. J. Eswaran, A. Horvath, S. Godbole et al., “RNA sequencing of cancer reveals novel splicing alterations,” Scientific Reports, vol. 3, article 1689, 2013. View at Google Scholar
  41. J. P. Venables, “Unbalanced alternative splicing and its significance in cancer,” Bioessays, vol. 28, no. 4, pp. 378–386, 2006. View at Publisher · View at Google Scholar · View at Scopus
  42. A. Relógio, C. Ben-Dov, M. Baum et al., “Alternative splicing microarrays reveal functional expression of neuron-specific regulators in Hodgkin lymphoma cells,” The Journal of Biological Chemistry, vol. 280, no. 6, pp. 4779–4784, 2005. View at Publisher · View at Google Scholar · View at Scopus
  43. R. Klinck, A. Bramard, L. Inkel et al., “Multiple alternative splicing markers for ovarian cancer,” Cancer Research, vol. 68, no. 3, pp. 657–663, 2008. View at Publisher · View at Google Scholar · View at Scopus
  44. C. Ghigna, C. Valacca, and G. Biamonti, “Alternative splicing and tumor progression,” Current Genomics, vol. 9, no. 8, pp. 556–570, 2008. View at Publisher · View at Google Scholar · View at Scopus
  45. C. J. David and J. L. Manley, “Alternative pre-mRNA splicing regulation in cancer: pathways and programs unhinged,” Genes and Development, vol. 24, no. 21, pp. 2343–2364, 2010. View at Publisher · View at Google Scholar · View at Scopus
  46. J. P. Venables, “Aberrant and alternative splicing in cancer,” Cancer Research, vol. 64, no. 21, pp. 7647–7654, 2004. View at Publisher · View at Google Scholar · View at Scopus
  47. Z. Kalniņa, P. Zayakin, K. Siliņa, and A. Line, “Alterations of pre-mRNA splicing in cancer,” Genes Chromosomes and Cancer, vol. 42, no. 4, pp. 342–357, 2005. View at Publisher · View at Google Scholar · View at Scopus
  48. A. Srebrow and A. R. Kornblihtt, “The connection between splicing and cancer,” Journal of Cell Science, vol. 119, no. 13, pp. 2635–2641, 2006. View at Publisher · View at Google Scholar · View at Scopus
  49. C. A. Pettigrew and M. A. Brown, “Pre-mRNA splicing aberrations and cancer,” Frontiers in Bioscience, vol. 13, no. 3, pp. 1090–1105, 2008. View at Publisher · View at Google Scholar · View at Scopus
  50. A. R. Grosso, S. Martins, and M. Carmo-Fonseca, “The emerging role of splicing factors in cancer,” EMBO Reports, vol. 9, no. 11, pp. 1087–1093, 2008. View at Publisher · View at Google Scholar · View at Scopus
  51. C. Ghigna, M. Moroni, C. Porta, S. Riva, and G. Biamonti, “Altered expression of heterogeneous nuclear ribonucleoproteins and SR factors in human colon adenocarcinomas,” Cancer Research, vol. 58, no. 24, pp. 5818–5824, 1998. View at Google Scholar · View at Scopus
  52. L. K. Zerbe, I. Pino, R. Pio et al., “Relative amounts of antagonistic splicing factors, hnRNP A1 and ASF/SF2, change during neoplastic lung growth: implications for pre-mRNA processing,” Molecular Carcinogenesis, vol. 41, no. 4, pp. 187–196, 2004. View at Publisher · View at Google Scholar · View at Scopus
  53. R. Karni, E. De Stanchina, S. W. Lowe, R. Sinha, D. Mu, and A. R. Krainer, “The gene encoding the splicing factor SF2/ASF is a proto-oncogene,” Nature Structural and Molecular Biology, vol. 14, no. 3, pp. 185–193, 2007. View at Publisher · View at Google Scholar · View at Scopus
  54. R. A. Padgett, “New connections between splicing and human disease,” Trends in Genetics, vol. 28, no. 4, pp. 147–154, 2012. View at Publisher · View at Google Scholar · View at Scopus
  55. Y. Fu, B. Huang, Z. Shi et al., “SRSF1 and SRSF9 RNA binding proteins promote Wnt signalling-mediated tumorigenesis by enhancing beta-catenin biosynthesis,” EMBO Molecular Medicine, vol. 5, pp. 737–750, 2013. View at Google Scholar
  56. M. Hirschfeld, M. Jaeger, E. Buratti et al., “Expression of tumor-promoting Cyr61 is regulated by hTRA2-β1 and acidosis,” Human Molecular Genetics, vol. 20, no. 12, pp. 2356–2365, 2011. View at Publisher · View at Google Scholar · View at Scopus
  57. L. H. Boise, M. Gonzalez-Garcia, C. E. Postema et al., “bcl-x, a bcl-2-related gene that functions as a dominant regulator of apoptotic cell death,” Cell, vol. 74, no. 4, pp. 597–608, 1993. View at Publisher · View at Google Scholar · View at Scopus
  58. D. Garneau, T. Revil, J. F. Fisette, and B. Chabot, “Heterogeneous nuclear ribonucleoprotein F/H proteins modulate the alternative splicing of the apoptotic mediator Bcl-x,” The Journal of Biological Chemistry, vol. 280, no. 24, pp. 22641–22650, 2005. View at Publisher · View at Google Scholar · View at Scopus
  59. A. Massiello, J. R. Roesser, and C. E. Chalfant, “SAP155 binds to ceramide-responsive RNA cis-element 1 and regulates the alternative 5′ splice site selection of Bcl-x pre-mRNA,” The FASEB Journal, vol. 20, no. 10, pp. 1680–1682, 2006. View at Publisher · View at Google Scholar · View at Scopus
  60. P. Cloutier, J. Toutant, L. Shkreta, S. Goekjian, T. Revil, and B. Chabot, “Antagonistic effects of the SRp30c protein and cryptic 5′ splice sites on the alternative splicing of the apoptotic regulator Bcl-x,” The Journal of Biological Chemistry, vol. 283, no. 31, pp. 21315–21324, 2008. View at Publisher · View at Google Scholar · View at Scopus
  61. T. Revil, J. Toutant, L. Shkreta, D. Garneau, P. Cloutier, and B. Chabot, “Protein kinase C-dependent control of Bcl-x alternative splicing,” Molecular and Cellular Biology, vol. 27, no. 24, pp. 8431–8441, 2007. View at Publisher · View at Google Scholar · View at Scopus
  62. M. Montes, A. Cloutier, N. Sánchez-Hernández et al., “TCERG1 regulates alternative splicing of the Bcl-x gene by modulating the rate of RNA polymerase II transcription,” Molecular and Cellular Biology, vol. 32, no. 4, pp. 751–762, 2012. View at Publisher · View at Google Scholar · View at Scopus
  63. L. Michelle, A. Cloutier, J. Toutant et al., “Proteins associated with the exon junction complex also control the alternative splicing of apoptotic regulators,” Molecular and Cellular Biology, vol. 32, no. 5, pp. 954–967, 2012. View at Publisher · View at Google Scholar · View at Scopus
  64. E. Stickeler, F. Kittrell, D. Medina, and S. M. Berget, “Stage-specific changes in SR splicing factors and alternative splicing in mammary tumorigenesis,” Oncogene, vol. 18, no. 24, pp. 3574–3582, 1999. View at Publisher · View at Google Scholar · View at Scopus
  65. A. Scorilas, L. Kyriakopoulou, D. Katsaros, and E. P. Diamandis, “Cloning of a gene (SR-A1), encoding for a new member of the human Ser/Arg-rich family of pre-mRNA splicing factors: overexpression in aggressive ovarian cancer,” British Journal of Cancer, vol. 85, no. 2, pp. 190–198, 2001. View at Publisher · View at Google Scholar · View at Scopus
  66. H. Sun and L. A. Chasin, “Multiple splicing defects in an intronic false exon,” Molecular and Cellular Biology, vol. 20, no. 17, pp. 6414–6425, 2000. View at Publisher · View at Google Scholar · View at Scopus
  67. M. Sironi, G. Menozzi, L. Riva et al., “Silencer elements as possible inhibitors of pseudoexon splicing,” Nucleic Acids Research, vol. 32, no. 5, pp. 1783–1791, 2004. View at Publisher · View at Google Scholar · View at Scopus
  68. X. H. F. Zhang and L. A. Chasin, “Computational definition of sequence motifs governing constitutive exon splicing,” Genes and Development, vol. 18, no. 11, pp. 1241–1250, 2004. View at Publisher · View at Google Scholar · View at Scopus
  69. W. G. Fairbrother and L. A. Chasin, “Human genomic sequences that inhibit splicing,” Molecular and Cellular Biology, vol. 20, no. 18, pp. 6816–6825, 2000. View at Publisher · View at Google Scholar · View at Scopus
  70. X. H. F. Zhang, C. S. Leslie, and L. A. Chasin, “Dichotomous splicing signals in exon flanks,” Genome Research, vol. 15, no. 6, pp. 768–779, 2005. View at Publisher · View at Google Scholar · View at Scopus
  71. E. Buratti, A. Dhir, M. A. Lewandowska, and F. E. Baralle, “RNA structure is a key regulatory element in pathology ATM and CFTR pseudoexon inclusion events,” Nucleic Acids Research, vol. 35, no. 13, pp. 4369–4383, 2007. View at Publisher · View at Google Scholar · View at Scopus
  72. A. Dhir, E. Buratti, M. A. Van Santen, R. Lührmann, and F. E. Baralle, “The intronic splicing code: multiple factors involved in ATM pseudoexon definition,” The EMBO Journal, vol. 29, no. 4, pp. 749–760, 2010. View at Publisher · View at Google Scholar · View at Scopus
  73. I. Scheinin, S. Myllykangas, I. Borze, T. Böhling, S. Knuutila, and J. Saharinen, “CanGEM: mining gene copy number changes in cancer,” Nucleic Acids Research, vol. 36, no. 1, pp. D830–D835, 2008. View at Publisher · View at Google Scholar · View at Scopus
  74. G. K. Hu, S. J. Madore, B. Moldover et al., “Predicting splice variant from DNA chip expression data,” Genome Research, vol. 11, no. 7, pp. 1237–1345, 2001. View at Publisher · View at Google Scholar · View at Scopus
  75. W. Fan, N. Khalid, A. R. Hallahan, J. M. Olson, and P. Z. Lue, “A statistical method for predicting splice variants between two groups of samples using GeneChip expression array data,” Theoretical Biology and Medical Modelling, vol. 3, article 19, 2006. View at Publisher · View at Google Scholar · View at Scopus
  76. M. Raponi, E. Buratti, M. Llorian, C. Stuani, C. W. J. Smith, and D. Baralle, “Polypyrimidine tract binding protein regulates alternative splicing of an aberrant pseudoexon in NF1,” FEBS Journal, vol. 275, no. 24, pp. 6101–6108, 2008. View at Publisher · View at Google Scholar · View at Scopus
  77. E. J. Wagner and M. A. Garcia-Blanco, “Minireview: polypyrimidine tract binding protein antagonizes exon definition,” Molecular and Cellular Biology, vol. 21, no. 10, pp. 3281–3288, 2001. View at Publisher · View at Google Scholar · View at Scopus
  78. I. Spier, S. Horpaopan, S. Vogt et al., “Deep intronic APC mutations explain a substantial proportion of patients with familial or early-onset adenomatous polyposis,” Human Mutation, vol. 33, no. 7, pp. 1045–1050, 2012. View at Publisher · View at Google Scholar · View at Scopus
  79. K. Nakamura, L. Du, R. Tunuguntla et al., “Functional characterization and targeted correction of atm mutations identified in japanese patients with ataxia-telangiectasia,” Human Mutation, vol. 33, no. 1, pp. 198–208, 2012. View at Publisher · View at Google Scholar · View at Scopus
  80. F. Pagani, E. Buratti, C. Stuani, R. Bendix, T. Dörk, and F. E. Baralle, “A new type of mutation causes a splicing defect in ATM,” Nature Genetics, vol. 30, no. 4, pp. 426–429, 2002. View at Publisher · View at Google Scholar · View at Scopus
  81. C. M. McConville, T. Stankovic, P. J. Byrd et al., “Mutations associated with variant phenotypes in ataxia-telangiectasia,” American Journal of Human Genetics, vol. 59, no. 2, pp. 320–330, 1996. View at Google Scholar · View at Scopus
  82. S. Cavalieri, E. Pozzi, R. A. Gatti, and A. Brusco, “Deep-intronic ATM mutation detected by genomic resequencing and corrected in vitro by antisense morpholino oligonucleotide (AMO),” European Journal of Human Genetics, vol. 21, no. 7, pp. 774–778, 2013. View at Publisher · View at Google Scholar
  83. N. Sorel, C. Mayeur-Rousse, S. Deverrière et al., “Comprehensive characterization of a novel intronic pseudo-exon inserted within an e14/a2 BCR-ABL rearrangement in a patient with chronic myeloid leukemia,” Journal of Molecular Diagnostics, vol. 12, no. 4, pp. 520–524, 2010. View at Publisher · View at Google Scholar · View at Scopus
  84. J. Laudadio, M. W. N. Deininger, M. J. Mauro, B. J. Druker, and R. D. Press, “An intron-derived insertion/truncation mutation in the BCR-ABL kinase domain in chronic myeloid leukemia patients undergoing kinase inhibitor therapy,” Journal of Molecular Diagnostics, vol. 10, no. 2, pp. 177–180, 2008. View at Publisher · View at Google Scholar · View at Scopus
  85. N. B. Quigley, D. C. Henley, R. A. Hubbard, J. Laudadio, and R. D. Press, “ABL kinase domain pseudoexon insertion is not uncommon in BCR-ABL transcripts,” Journal of Molecular Diagnostics, vol. 10, no. 5, pp. 475–476, 2008. View at Publisher · View at Google Scholar · View at Scopus
  86. V. Balz, H. B. Prisack, H. Bier, and H. Bojar, “Analysis of BRCA1, TP53, and TSG101 germline mutations in German breast and/or ovarian cancer families,” Cancer Genetics and Cytogenetics, vol. 138, no. 2, pp. 120–127, 2002. View at Publisher · View at Google Scholar · View at Scopus
  87. X. Chen, T. T. N. Truong, J. Weaver et al., “Intronic alterations in BRCA1 and BRCA2: effect on mRNA splicing fidelity and expression,” Human Mutation, vol. 27, no. 5, pp. 427–435, 2006. View at Publisher · View at Google Scholar · View at Scopus
  88. O. Anczukow, M. Buisson, M. Leone et al., “BRCA2 deep intronic mutation causing activation of a cryptic exon: opening toward a new preventive therapeutic strategy,” Clinical Cancer Research, vol. 18, pp. 4903–4909, 2012. View at Google Scholar
  89. M. Wang, H. Dotzlaw, S. A. W. Fuqua, and L. C. Murphy, “A point mutation in the human estrogen receptor gene is associated with the expression of an abnormal estrogen receptor mRNA containing a 69 novel nucleotide insertion,” Breast Cancer Research and Treatment, vol. 44, no. 2, pp. 145–151, 1997. View at Publisher · View at Google Scholar · View at Scopus
  90. M. Clendenning, D. D. Buchanan, M. D. Walsh et al., “Mutation deep within an intron of MSH2 causes Lynch syndrome,” Familial Cancer, vol. 10, no. 2, pp. 297–301, 2011. View at Publisher · View at Google Scholar · View at Scopus
  91. J. Fernández-Rodríguez, J. Castellsagué, L. Benito et al., “A mild neurofibromatosis type 1 phenotype produced by the combination of the benign nature of a leaky NF1-splice mutation and the presence of a complex mosaicism,” Human Mutation, vol. 32, no. 7, pp. 705–709, 2011. View at Publisher · View at Google Scholar · View at Scopus
  92. E. Pros, J. Fernández-Rodríguez, B. Canet et al., “Antisense therapeutics for neurofibromatosis type 1 caused by deep intronic mutations,” Human Mutation, vol. 30, no. 3, pp. 454–462, 2009. View at Publisher · View at Google Scholar · View at Scopus
  93. M. Raponi, M. Upadhyaya, and D. Baralle, “Functional splicing assay shows a pathogenic intronic mutation in neurofibromatosis type 1 (NF1) due to intronic sequence exonization,” Human mutation, vol. 27, no. 3, pp. 294–295, 2006. View at Google Scholar · View at Scopus
  94. E. Pros, C. Gómez, T. Martín, P. Fábregas, E. Serra, and C. Lázaro, “Nature and mRNA effect of 282 different NF1 point mutations: focus on splicing alterations,” Human mutation, vol. 29, no. 9, pp. E173–E193, 2008. View at Publisher · View at Google Scholar · View at Scopus
  95. K. Wimmer, X. Roca, H. Beiglböck et al., “Extensive in silico analysis of NF1 splicing defects uncovers determinants for splicing outcome upon 5′ splice-site disruption,” Human Mutation, vol. 28, no. 6, pp. 599–612, 2007. View at Publisher · View at Google Scholar · View at Scopus
  96. G. Perrin, M. A. Morris, S. E. Antonarakis, E. Boltshauser, and P. Hutter, “Two novel mutations affecting mRNA splicing of the neurofibromatosis type 1 (NF1) gene,” Human Mutation, vol. 7, pp. 172–175, 1996. View at Google Scholar
  97. E. Ars, E. Serra, J. Garcia et al., “Mutations affecting mRNA splicing are the most common molecular defects in patients with neurofibromatosis type 1,” Human Molecular Genetics, vol. 9, no. 2, pp. 237–247, 2000. View at Google Scholar
  98. A. de Klein, P. H. J. Riegman, E. K. Bijlsma et al., “A G→A transition creates a branch point sequence and activation of a cryptic exon, resulting in the hereditary disorder neurofibromatosis 2,” Human Molecular Genetics, vol. 7, no. 3, pp. 393–398, 1998. View at Publisher · View at Google Scholar · View at Scopus
  99. C. Dehainault, D. Michaux, S. Pagès-Berhouet et al., “A deep intronic mutation in the RB1 gene leads to intronic sequence exonisation,” European Journal of Human Genetics, vol. 15, no. 4, pp. 473–477, 2007. View at Publisher · View at Google Scholar · View at Scopus
  100. K. Mayer, W. Ballhausen, W. Leistner, and H. D. Rott, “Three novel types of splicing aberrations in the tuberous sclerosis TSC2 gene caused by mutations apart from splice consensus sequences,” Biochimica et Biophysica Acta, vol. 1502, no. 3, pp. 495–507, 2000. View at Publisher · View at Google Scholar · View at Scopus
  101. M. V. Masala, S. Scapaticci, C. Olivieri et al., “Epidemiology and clinical aspects of Werner's syndrome in North Sardinia: description of a cluster,” European Journal of Dermatology, vol. 17, no. 3, pp. 213–216, 2007. View at Google Scholar
  102. K. Friedrich, L. Lee, D. F. Leistritz et al., “WRN mutations in Werner syndrome patients: genomic rearrangements, unusual intronic mutations and ethnic-specific alterations,” Human Genetics, vol. 128, no. 1, pp. 103–111, 2010. View at Publisher · View at Google Scholar · View at Scopus
  103. S. E. Flanagan, W. Xie, R. Caswell et al., “Next-generation sequencing reveals deep intronic cryptic ABCC8 and HADH splicing founder mutations causing hyperinsulinism by pseudoexon activation,” The American Journal of Human Genetics, vol. 92, pp. 131–136, 2013. View at Google Scholar
  104. M. Milh, A. Pop, W. Kanhai et al., “Atypical pyridoxine-dependent epilepsy due to a pseudoexon in ALDH7A1,” Molecular Genetics and Metabolism, vol. 105, no. 4, pp. 684–686, 2012. View at Publisher · View at Google Scholar · View at Scopus
  105. W. I. Lee, T. R. Torgerson, M. J. Schumacher, L. Yel, Q. Zhu, and H. D. Ochs, “Molecular analysis of a large cohort of patients with the hyper immunoglobulin M (IgM) syndrome,” Blood, vol. 105, no. 5, pp. 1881–1890, 2005. View at Publisher · View at Google Scholar · View at Scopus
  106. A. I. den Hollander, R. K. Koenekoop, S. Yzer et al., “Mutations in the CEP290 (NPHP6) gene are a frequent cause of Leber congenital amaurosis,” American Journal of Human Genetics, vol. 79, pp. 556–561, 2006. View at Google Scholar
  107. R. W. Collin, A. I. den Hollander, S. D. van der Velde-Visser, J. Bennicelli, J. Bennett, and F. P. Cremers, “Antisense Oligonucleotide (AON)-based Therapy for Leber Congenital Amaurosis caused by a Frequent Mutation in CEP290,” Molecular Therapy, vol. 1, article e14, 2012. View at Google Scholar
  108. J. A. J. M. van den Hurk, D. J. R. van de Pol, B. Wissinger et al., “Novel types of mutation in the choroideremia (CHM) gene: a full-length L1 insertion and an intronic mutation activating a cryptic exon,” Human Genetics, vol. 113, no. 3, pp. 268–275, 2003. View at Publisher · View at Google Scholar · View at Scopus
  109. B. Knebelmann, L. Forestier, L. Drouot et al., “Splice-mediated insertion of an Alu sequence in the COL4A3 mRNA causing autosomal recessive Alport syndrome,” Human Molecular Genetics, vol. 4, no. 4, pp. 675–679, 1995. View at Google Scholar · View at Scopus
  110. N. Akawi, L. Al-Gazali, and B. R. Ali, “Clinical and molecular analysis of UAE fibrochondrogenesis patients expands the phenotype and reveals two COL11A1 homozygous null mutations,” Clinical Genetics, vol. 82, pp. 147–156, 2012. View at Publisher · View at Google Scholar · View at Scopus
  111. R. Varon, R. Gooding, C. Steglich et al., “Partial deficiency of the C-terminal-domain phosphatase of RNA polymerase II is associated with congenital cataracts facial dysmorphism neuropathy syndrome,” Nature Genetics, vol. 35, no. 2, pp. 185–189, 2003. View at Publisher · View at Google Scholar · View at Scopus
  112. A. Rump, A. Rösen-Wolff, M. Gahr et al., “A splice-supporting intronic mutation in the last bp position of a cryptic exon within intron 6 of the CYBB gene induces its incorporation into the mRNA causing chronic granulomatous disease (CGD),” Gene, vol. 371, no. 2, pp. 174–181, 2006. View at Publisher · View at Google Scholar · View at Scopus
  113. D. Noack, P. G. Heyworth, P. E. Newburger, and A. R. Cross, “An unusual intronic mutation in the CYBB gene giving rise to chronic granulomatous disease,” Biochimica et Biophysica Acta, vol. 1537, no. 2, pp. 125–131, 2001. View at Publisher · View at Google Scholar · View at Scopus
  114. D. Y. Hwang, C. C. Hung, F. G. Riepe et al., “CYP17A1 intron mutation causing cryptic splicing in 17α-hydroxylase deficiency,” PloS ONE, vol. 6, article e25492, no. 9, 2011. View at Publisher · View at Google Scholar · View at Scopus
  115. H. Ikeda, Y. Matsubara, H. Mikami et al., “Molecular analysis of dihydropteridine reductase deficiency: identification of two novel mutations in Japanese patients,” Human Genetics, vol. 100, no. 5-6, pp. 637–642, 1997. View at Publisher · View at Google Scholar · View at Scopus
  116. A. B. P. van Kuilenburg, J. Meijer, A. N. P. M. Mul et al., “Intragenic deletions and a deep intronic mutation affecting pre-mRNA splicing in the dihydropyrimidine dehydrogenase gene as novel mechanisms causing 5-fluorouracil toxicity,” Human Genetics, vol. 128, no. 5, pp. 529–538, 2010. View at Publisher · View at Google Scholar · View at Scopus
  117. D. C. Guo, P. Gupta, V. Tran-Fadulu et al., “An FBN1 pseudoexon mutation in a patient with Marfan syndrome: confirmation of cryptic mutations leading to disease,” Journal of Human Genetics, vol. 53, no. 11-12, pp. 1007–1011, 2008. View at Publisher · View at Google Scholar · View at Scopus
  118. L. A. Metherell, S. A. Akker, P. B. Munroe et al., “Pseudoexon activation as a novel mechanism for disease resulting in atypical growth-hormone insensitivity,” American Journal of Human Genetics, vol. 69, no. 3, pp. 641–646, 2001. View at Publisher · View at Google Scholar · View at Scopus
  119. S. A. Akker, S. Misra, S. Aslam et al., “Pre-spliceosomal binding of U1 small nuclear ribonucleoprotein (RNP) and heterogenous nuclear RNP E1 is associated with suppression of a growth hormone receptor pseudoexon,” Molecular Endocrinology, vol. 21, no. 10, pp. 2529–2540, 2007. View at Publisher · View at Google Scholar · View at Scopus
  120. R. Vervoort, R. Gitzelmann, W. Lissens, and I. Liebaers, “A mutation (IVS8+0.6kbdelTC) creating a new donor splice site activates a cryptic exon in an Alu-element in intron 8 of the human β-glucuronidase gene,” Human Genetics, vol. 103, no. 6, pp. 686–693, 1998. View at Publisher · View at Google Scholar · View at Scopus
  121. J. Purevsuren, T. Fukao, Y. Hasegawa, S. Fukuda, H. Kobayashi, and S. Yamaguchi, “Study of deep intronic sequence exonization in a Japanese neonate with a mitochondrial trifunctional protein deficiency,” Molecular Genetics and Metabolism, vol. 95, no. 1-2, pp. 46–51, 2008. View at Publisher · View at Google Scholar · View at Scopus
  122. N. Sévenet, A. Lellouch-Tubiana, D. Schofield et al., “Spectrum of hSNF5/INI1 somatic mutations in human cancer and genotype-phenotype correlations,” Human Molecular Genetics, vol. 8, no. 13, pp. 2359–2368, 1999. View at Google Scholar · View at Scopus
  123. A. Olsson, L. Lind, L. E. Thornell, and M. Holmberg, “Myopathy with lactic acidosis is linked to chromosome 12q23.3-24.11 and caused by an intron mutation in the ISCU gene resulting in a splicing defect,” Human Molecular Genetics, vol. 17, no. 11, pp. 1666–1672, 2008. View at Publisher · View at Google Scholar · View at Scopus
  124. F. Mochel, M. A. Knight, W. H. Tong et al., “Splice mutation in the Iron-Sulfur cluster scaffold protein ISCU causes myopathy with exercise intolerance,” American Journal of Human Genetics, vol. 82, no. 3, pp. 652–660, 2008. View at Publisher · View at Google Scholar · View at Scopus
  125. G. Kollberg, M. Tulinius, A. Melberg et al., “Clinical manifestation and a new ISCU mutation in ironsulphur cluster deficiency myopathy,” Brain, vol. 132, no. 8, pp. 2170–2179, 2009. View at Publisher · View at Google Scholar · View at Scopus
  126. N. Lucien, J. Chiaroni, J. P. Cartron, and P. Bailly, “Partial deletion in the JK locus causing a JK(null) phenotype,” Blood, vol. 99, no. 3, pp. 1079–1081, 2002. View at Publisher · View at Google Scholar · View at Scopus
  127. M. Stucki, T. Suormala, B. Fowler, D. Valle, and M. R. Baumgartner, “Cryptic exon activation by disruption of exon splice enhancer: a novel mechanism causing 3-methyl crotonyl-CoA carboxylase deficiency,” The Journal of Biological Chemistry, vol. 284, no. 42, pp. 28953–28957, 2009. View at Publisher · View at Google Scholar · View at Scopus
  128. H. Yamaguchi, T. Fujimoto, S. Nakamura et al., “Aberrant splicing of the milk fat globule-EGF factor 8 (MFG-E8) gene in human systemic lupus erythematosus,” European Journal of Immunology, vol. 40, no. 6, pp. 1778–1785, 2010. View at Publisher · View at Google Scholar · View at Scopus
  129. C. Mancini, G. Vaula, L. Scalzitti et al., “Megalencephalic leukoencephalopathy with subcortical cysts type 1 (MLC1) due to a homozygous deep intronic splicing mutation (c.895-226T>G) abrogated in vitro using an antisense morpholino oligonucleotide,” Neurogenetics, vol. 13, no. 3, pp. 205–214, 2012. View at Publisher · View at Google Scholar · View at Scopus
  130. K. Homolova, P. Zavadakova, T. K. Doktor, L. D. Schroeder, V. Kozich, and B. S. Andresen, “The deep intronic c.903+469T > C mutation in the MTRR gene creates an SF2/ASF binding exonic splicing enhancer, which leads to pseudoexon activation and causes the cblE type of homocystinuria,” Human Mutation, vol. 31, no. 4, pp. 437–444, 2010. View at Publisher · View at Google Scholar · View at Scopus
  131. F. Vetrini, R. Tammaro, S. Bondanza et al., “Aberrant splicing in the ocular albinism type 1 gene (OA1/GPR143) is corrected in vitro by morpholino antisense oligonucleotides,” Human Mutation, vol. 27, no. 5, pp. 420–426, 2006. View at Publisher · View at Google Scholar · View at Scopus
  132. G. A. Mitchell, D. Labuda, G. Fontaine et al., “Splice-mediated insertion of an Alu sequence inactivates ornithine δ-aminotransferase: a role for Alu elements in human mutation,” Proceedings of the National Academy of Sciences of the United States of America, vol. 88, no. 3, pp. 815–819, 1991. View at Publisher · View at Google Scholar · View at Scopus
  133. T. R. Webb, D. A. Parfitt, J. C. Gardner et al., “Deep intronic mutation in OFD1, identified by targeted genomic next-generation sequencing, causes a severe form of X-linked retinitis pigmentosa (RP23),” Human Molecular Genetics, vol. 21, pp. 3647–3654, 2012. View at Google Scholar
  134. W. Ogino, Y. Takeshima, A. Nishiyama et al., “Mutation analysis of the ornithine transcarbamylase (OTC) gene in five Japanese OTC deficiency patients revealed two known and three novel mutations including a deep intronic mutation,” Kobe Journal of Medical Sciences, vol. 53, no. 5, pp. 229–240, 2007. View at Google Scholar · View at Scopus
  135. A. Rincón, C. Aguado, L. R. Desviat, R. Sánchez-Alcudia, M. Ugarte, and B. Pérez, “Propionic and methylmalonic acidemia: antisense therapeutics for intronic variations causing aberrantly spliced messenger RNA,” American Journal of Human Genetics, vol. 81, no. 6, pp. 1262–1270, 2007. View at Publisher · View at Google Scholar · View at Scopus
  136. P. T. Christie, B. Harding, M. A. Nesbit, M. P. Whyte, and R. V. Thakker, “X-linked hypophosphatemia attributable to pseudoexons of the PHEX gene,” Journal of Clinical Endocrinology and Metabolism, vol. 86, no. 8, pp. 3840–3844, 2001. View at Publisher · View at Google Scholar · View at Scopus
  137. L. Michel-Calemard, F. Dijoud, M. Till et al., “Pseudoexon activation in the PKHD1 gene: a French founder intronic mutation IVS46+653A>G causing severe autosomal recessive polycystic kidney disease,” Clinical Genetics, vol. 75, no. 2, pp. 203–206, 2009. View at Publisher · View at Google Scholar · View at Scopus
  138. A. I. Vega, C. Perez-Cerda, L. R. Desviat, G. Matthijs, M. Ugarte, and B. Pérez, “Functional analysis of three splicing mutations identified in the PMM2 gene: toward a new therapy for congenital disorder of glycosylation type IA,” Human Mutation, vol. 30, no. 5, pp. 795–803, 2009. View at Publisher · View at Google Scholar · View at Scopus
  139. E. Schollen, L. Keldermans, F. Foulquier et al., “Characterization of two unusual truncating PMM2 mutations in two CDG-Ia patients,” Molecular Genetics and Metabolism, vol. 90, no. 4, pp. 408–413, 2007. View at Publisher · View at Google Scholar · View at Scopus
  140. T. R. Frio, T. L. McGee, N. M. Wade et al., “A single-base substitution within an intronic repetitive element causes dominant retinitis pigmentosa with reduced penetrance,” Human Mutation, vol. 30, no. 9, pp. 1340–1347, 2009. View at Publisher · View at Google Scholar · View at Scopus
  141. H. C. Liu, H. L. Eng, Y. F. Yang et al., “Aberrant RNA splicing in RHD 7-9 exons of DEL individuals in Taiwan: A Mechanism Study,” Biochimica et Biophysica Acta, vol. 1800, no. 6, pp. 565–573, 2010. View at Publisher · View at Google Scholar · View at Scopus
  142. N. Monnier, A. Ferreiro, I. Marty, A. Labarre-Villa, P. Mezin, and J. Lunardi, “A homozygous splicing mutation causing a depletion of skeletal muscle RYR1 is associated with multi-minicore disease congenital myopathy with ophthalmoplegia,” Human Molecular Genetics, vol. 12, no. 10, pp. 1171–1178, 2003. View at Publisher · View at Google Scholar · View at Scopus
  143. K. Nozu, K. Iijima, Y. Nozu et al., “A deep intronic mutation in the SLC12A3 gene leads to gitelman syndrome,” Pediatric Research, vol. 66, no. 5, pp. 590–593, 2009. View at Publisher · View at Google Scholar · View at Scopus
  144. C. Vaché, T. Besnard, P. le Berre et al., “Usher syndrome type 2 caused by activation of an USH2A pseudoexon: implications for diagnosis and therapy,” Human Mutation, vol. 33, no. 1, pp. 104–108, 2012. View at Publisher · View at Google Scholar · View at Scopus
  145. E. Ruoslahti, “Fibronectin and its receptors,” Annual Review of Biochemistry, vol. 57, pp. 375–413, 1988. View at Google Scholar · View at Scopus
  146. E. S. White, F. E. Baralle, and A. F. Muro, “New insights into form and function of fibronectin splice variants,” Journal of Pathology, vol. 216, no. 1, pp. 1–14, 2008. View at Publisher · View at Google Scholar · View at Scopus
  147. K. Vibe-Pedersen, S. Magnusson, and F. E. Baralle, “Donor and acceptor splice signals within an exon of the human fibronectin gene: a new type of differential splicing,” FEBS Letters, vol. 207, no. 2, pp. 287–291, 1986. View at Google Scholar · View at Scopus
  148. R. P. Hershberger and L. A. Culp, “Cell-type-specific expression of alternatively spliced human fibronectin IIICS mRNAs,” Molecular and Cellular Biology, vol. 10, no. 2, pp. 662–671, 1990. View at Google Scholar · View at Scopus
  149. A. P. Mould and M. J. Humphries, “Identification of a novel recognition sequence for the integrin α4β1 in the COOH-terminal heparin-binding domain of fibronectin,” The EMBO Journal, vol. 10, no. 13, pp. 4089–4095, 1991. View at Google Scholar · View at Scopus
  150. M. J. Humphries, A. Komoriya, and S. K. Akiyama, “Identification of two distinct regions of the type III connecting segment of human plasma fibronectin that promote cell type-specific adhesion,” The Journal of Biological Chemistry, vol. 262, no. 14, pp. 6886–6892, 1987. View at Google Scholar · View at Scopus
  151. A. P. Mould, J. A. Askari, S. E. Craig, A. N. Garratt, J. Clements, and M. J. Humphries, “Integrin α4β1-mediated melanoma cell adhesion and migration on vascular cell adhesion molecule-1 (VCAM-1) and the alternatively spliced IIICS region of fibronectin,” The Journal of Biological Chemistry, vol. 269, no. 44, pp. 27224–27230, 1994. View at Google Scholar · View at Scopus
  152. T. Kumazaki, Y. Mitsui, K. Hamada, H. Sumida, and M. Nishiyama, “Detection of alternative splicing of fibronectin mRNA in a single cell,” Journal of Cell Science, vol. 112, part 10, no. 10, pp. 1449–1453, 1999. View at Google Scholar · View at Scopus
  153. K. P. Schofield and M. J. Humphries, “Identification of fibronectin IIICS variants in human bone marrow stroma,” Blood, vol. 93, no. 1, pp. 410–411, 1999. View at Google Scholar · View at Scopus
  154. U. Trefzer, Y. Chen, G. Herberth et al., “The monoclonal antibody SM5-1 recognizes a fibronectin variant which is widely expressed in melanoma,” BMC Cancer, vol. 6, article 8, 2006. View at Publisher · View at Google Scholar · View at Scopus
  155. H. J. Mardon and G. Sebastio, “Regulation of alternative splicing in the IIICS region of human fibronectin pre-mRNA encoding cell binding sites CS1 and CS5,” Journal of Cell Science, vol. 103, part 2, no. 2, pp. 423–433, 1992. View at Google Scholar · View at Scopus
  156. I. Silman and J. L. Sussman, “Acetylcholinesterase: “Classical” and “non-classical” functions and pharmacology,” Current Opinion in Pharmacology, vol. 5, no. 3, pp. 293–302, 2005. View at Publisher · View at Google Scholar · View at Scopus
  157. H. Soreq and S. Seidman, “Acetylcholinesterase—new roles for an old actor,” Nature Reviews Neuroscience, vol. 2, no. 4, pp. 294–302, 2001. View at Publisher · View at Google Scholar · View at Scopus
  158. J. Massoulié, “The origin of the molecular diversity and functional anchoring of cholinesterases,” NeuroSignals, vol. 11, no. 3, pp. 130–143, 2002. View at Publisher · View at Google Scholar · View at Scopus
  159. R. Y. Y. Chan, F. A. Adatia, A. M. Krupa, and B. J. Jasmin, “Increased expression of acetylcholinesterase T and R transcripts during hematopoietic differentiation is accompanied by parallel elevations in the levels of their respective molecular forms,” The Journal of Biological Chemistry, vol. 273, no. 16, pp. 9727–9733, 1998. View at Publisher · View at Google Scholar · View at Scopus
  160. N. A. Perrier, M. Salani, C. Falasca, S. Bon, G. Augusti-Tocco, and J. Massoulié, “The readthrough variant of acetylcholinesterase remains very minor after heat shock, organophosphate inhibition and stress, in cell culture and in vivo,” Journal of Neurochemistry, vol. 94, no. 3, pp. 629–638, 2005. View at Publisher · View at Google Scholar · View at Scopus
  161. D. Grisaru, M. Sternfeld, A. Eldor, D. Glick, and H. Soreq, “Structural roles of acetylcholinesterase variants in biology and pathology,” European Journal of Biochemistry, vol. 264, no. 3, pp. 672–686, 1999. View at Publisher · View at Google Scholar · View at Scopus
  162. E. Meshorer and H. Soreq, “Virtues and woes of AChE alternative splicing in stress-related neuropathologies,” Trends in Neurosciences, vol. 29, no. 4, pp. 216–224, 2006. View at Publisher · View at Google Scholar · View at Scopus
  163. C. Perry, E. H. Sklan, K. Birikh et al., “Complex regulation of acetylcholinesterase gene expression in human brain tumors,” Oncogene, vol. 21, no. 55, pp. 8428–8441, 2002. View at Publisher · View at Google Scholar · View at Scopus
  164. C. Perry, E. H. Sklan, and H. Soreq, “CREB regulates AChE-R-induced proliferation of human glioblastoma cells,” Neoplasia, vol. 6, no. 3, pp. 279–286, 2004. View at Google Scholar · View at Scopus
  165. I. Mor, T. Bruck, D. Greenberg et al., “Alternate AChE-R variants facilitate cellular metabolic activity and resistance to genotoxic stress through enolase and RACK1 interactions,” Chemico-Biological Interactions, vol. 175, no. 1–3, pp. 11–21, 2008. View at Publisher · View at Google Scholar · View at Scopus
  166. M. F. Montenegro, F. Ruiz-Espejo, F. J. Campoy et al., “Cholinesterases are down-expressed in human colorectal carcinoma,” Cellular and Molecular Life Sciences, vol. 63, no. 18, pp. 2175–2182, 2006. View at Publisher · View at Google Scholar · View at Scopus
  167. B. Li, H. Pan, J. C. Winkelmann, and W. Dai, “Thrombopoietin and its alternatively spliced form are expressed in human amygdala and hippocampus,” Blood, vol. 87, no. 12, pp. 5382–5384, 1996. View at Google Scholar · View at Scopus
  168. R. Sungaran, B. Markovic, and B. H. Chong, “Localization and regulation of thrombopoietin mRNA expression in human kidney, liver, bone marrow, and spleen using in situ hybridization,” Blood, vol. 89, no. 1, pp. 101–107, 1997. View at Google Scholar · View at Scopus
  169. C. Dame, E. M. Wolber, P. Freitag, D. Hofmann, P. Bartmann, and J. Fandrey, “Thrombopoietin gene expression in the developing human central nervous system,” Developmental Brain Research, vol. 143, no. 2, pp. 217–223, 2003. View at Publisher · View at Google Scholar · View at Scopus
  170. R. Marcucci and M. Romano, “Thrombopoietin and its splicing variants: structure and functions in thrombopoiesis and beyond,” Biochimica et Biophysica Acta, vol. 1782, no. 7-8, pp. 427–432, 2008. View at Publisher · View at Google Scholar · View at Scopus
  171. M. Romano, R. Marcucci, and F. E. Baralle, “Splicing of constitutive upstream introns is essential for the recognition of intra-exonic suboptimal splice sites in the thrombopoietin gene,” Nucleic Acids Research, vol. 29, no. 4, pp. 886–894, 2001. View at Google Scholar · View at Scopus
  172. T. Wada, Y. Nagata, H. Nagahisa et al., “Characterization of the truncated thrombopoietin variants,” Biochemical and Biophysical Research Communications, vol. 213, no. 3, pp. 1091–1098, 1995. View at Publisher · View at Google Scholar · View at Scopus
  173. R. C. Hoffman, H. Andersen, K. Walker et al., “Peptide, disulfide, and glycosylation mapping of recombinant human thrombopoietin from Ser1 to Arg246,” Biochemistry, vol. 35, no. 47, pp. 14849–14861, 1996. View at Publisher · View at Google Scholar · View at Scopus
  174. X. L. Wu, M. Nakayama, and J. W. Adamson, “Identification of five new isoforms of murine thrombopoietin mRNA,” Biochemical and Biophysical Research Communications, vol. 276, no. 1, pp. 137–143, 2000. View at Publisher · View at Google Scholar · View at Scopus
  175. Y. Sasaki, T. Takahashi, H. Miyazaki et al., “Production of thrombopoietin by human carcinomas and its novel isoforms,” Blood, vol. 94, no. 6, pp. 1952–1960, 1999. View at Google Scholar · View at Scopus
  176. S. Bonnal, L. Vigevani, and J. Valcarcel, “The spliceosome as a target of novel antitumour drugs,” Nature Reviews Drug Discovery, vol. 11, pp. 847–859, 2012. View at Google Scholar
  177. E. Zaharieva, J. K. Chipman, and M. Soller, “Alternative splicing interference by xenobiotics,” Toxicology, vol. 296, no. 1–3, pp. 1–12, 2012. View at Publisher · View at Google Scholar · View at Scopus
  178. F. Muntoni and M. J. A. Wood, “Targeting RNA to treat neuromuscular disease,” Nature Reviews Drug Discovery, vol. 10, no. 8, pp. 621–637, 2011. View at Publisher · View at Google Scholar · View at Scopus
  179. R. Kole, A. R. Krainer, and S. Altman, “RNA therapeutics: beyond RNA interference and antisense oligonucleotides,” Nature Reviews Drug Discovery, vol. 11, no. 2, pp. 125–140, 2012. View at Publisher · View at Google Scholar · View at Scopus
  180. A. Aartsma-Rus and G. J. B. Van Ommen, “Antisense-mediated exon skipping: a versatile tool with therapeutic and research applications,” RNA, vol. 13, no. 10, pp. 1609–1624, 2007. View at Publisher · View at Google Scholar · View at Scopus
  181. Z. Dominski and R. Kole, “Restoration of correct splicing in thalassemic pre-mRNA by antisense oligonucleotides,” Proceedings of the National Academy of Sciences of the United States of America, vol. 90, no. 18, pp. 8673–8677, 1993. View at Google Scholar · View at Scopus
  182. S. Kishore and S. Stamm, “The snoRNA HBII-52 regulates alternative splicing of the serotonin receptor 2C,” Science, vol. 311, no. 5758, pp. 230–232, 2006. View at Publisher · View at Google Scholar · View at Scopus
  183. A. Aartsma-Rus, L. van Vliet, M. Hirschi et al., “Guidelines for antisense oligonucleotide design and insight into splice-modulating mechanisms,” Molecular Therapy, vol. 17, no. 3, pp. 548–553, 2009. View at Publisher · View at Google Scholar · View at Scopus
  184. H. Heemskerk, C. L. De Winter, G. J. B. Van Ommen, J. C. T. Van Deutekom, and A. Aartsma-Rus, “Development of antisense-mediated exon skipping as a treatment for Duchenne muscular dystrophy,” Annals of the New York Academy of Sciences, vol. 1175, pp. 71–79, 2009. View at Publisher · View at Google Scholar · View at Scopus
  185. G. C. Kendall, E. I. Mokhonova, M. Moran et al., “Dantrolene enhances antisense-mediated exon skipping in human and mouse models of Duchenne muscular dystrophy,” Science Translational Medicine, vol. 4, no. 164, article 164ra160, 2012. View at Publisher · View at Google Scholar
  186. D. Gendron, S. Carriero, D. Garneau et al., “Modulation of 5′ splice site selection using tailed oligonucleotides carrying splicing signals,” BMC Biotechnology, vol. 6, article 5, 2006. View at Publisher · View at Google Scholar · View at Scopus
  187. M. A. Garcia-Blanco, A. P. Baraniak, and E. L. Lasda, “Alternative splicing in disease and therapy,” Nature Biotechnology, vol. 22, no. 5, pp. 535–546, 2004. View at Publisher · View at Google Scholar · View at Scopus
  188. M. Nissim-Rafinia, M. Aviram, S. H. Randell et al., “Restoration of the cystic fibrosis transmembrane conductance regulator function by splicing modulation,” EMBO Reports, vol. 5, no. 11, pp. 1071–1077, 2004. View at Publisher · View at Google Scholar · View at Scopus
  189. E. Pros, J. Fernández-Rodríguez, L. Benito et al., “Modulation of aberrant NF1 pre-mRNA splicing by kinetin treatment,” European Journal of Human Genetics, vol. 18, no. 5, pp. 614–617, 2010. View at Publisher · View at Google Scholar · View at Scopus
  190. T. Cermak, E. L. Doyle, M. Christian et al., “Efficient design and assembly of custom TALEN and other TAL effector-based constructs for DNA targeting,” Nucleic Acids Research, vol. 39, no. 12, article e82, 2011. View at Publisher · View at Google Scholar