About this Journal Submit a Manuscript Table of Contents
The Scientific World Journal
Volume 2013 (2013), Article ID 703568, 8 pages
http://dx.doi.org/10.1155/2013/703568
Review Article

Alternative Splicing for Diseases, Cancers, Drugs, and Databases

1Department of Radiation Oncology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
2Department of Radiation Oncology, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan
3Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan
4Department of Biotechnology, Kaohsiung Medical University, Kaohsiung 807, Taiwan
5Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
6Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung 807, Taiwan
7Bioresource Collection and Research Center, Food Industry Research and Development Institute, Hsinchu 300, Taiwan
8Institute of Biomedical Science, National Sun Yat-Sen University, Kaohsiung 807, Taiwan
9Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 807, Taiwan
10Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung 807, Taiwan

Received 1 April 2013; Accepted 30 April 2013

Academic Editors: F. Alvarez-Valin and A. Komiya

Copyright © 2013 Jen-Yang Tang 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. D. Brett, H. Pospisil, J. Valcárcel, J. Reich, and P. Bork, “Alternative splicing and genome complexity,” Nature Genetics, vol. 30, no. 1, pp. 29–30, 2002. View at Publisher · View at Google Scholar · View at Scopus
  2. C. Ghigna, M. De Toledo, S. Bonomi et al., “Pro-metastatic splicing of Ron proto-oncogene mRNA can be reversed: therapeutic potential of bifunctional oligonucleotides and indole derivatives,” RNA Biology, vol. 7, no. 4, pp. 495–503, 2010. View at Publisher · View at Google Scholar · View at Scopus
  3. K. F. Mittendorf, C. L. Deatherage, M. D. Ohi, and C. R. Sanders, “Tailoring of membrane proteins by alternative splicing of pre-mRNA,” Biochemistry, vol. 51, no. 28, pp. 5541–5556, 2012. View at Publisher · View at Google Scholar
  4. R. F. Luco, M. Allo, I. E. Schor, A. R. Kornblihtt, and T. Misteli, “Epigenetics in alternative pre-mRNA splicing,” Cell, vol. 144, no. 1, pp. 16–26, 2011. View at Publisher · View at Google Scholar · View at Scopus
  5. M. G. Poulos, R. Batra, K. Charizanis, and M. S. Swanson, “Developments in RNA splicing and disease,” Cold Spring Harbor Perspectives in Biology, vol. 3, no. 1, Article ID a000778, 2011. View at Publisher · View at Google Scholar · View at Scopus
  6. J. D. Mills and M. Janitz, “Alternative splicing of mRNA in the molecular pathology of neurodegenerative diseases,” Neurobiology of Aging, vol. 33, no. 5, pp. 1011–1024, 2012.
  7. 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
  8. R. H. Fu, S. P. Liu, S. J. Huang et al., “Aberrant alternative splicing events in Parkinson's disease,” Cell Transplantation, vol. 22, no. 4, pp. 653–661, 2013. View at Publisher · View at Google Scholar
  9. J. Pearn, “Classification of spinal muscular atrophies,” Lancet, vol. 1, no. 8174, pp. 919–922, 1980. View at Scopus
  10. J. Zhou, X. Zheng, and H. Shen, “Targeting RNA-splicing for SMA treatment,” Molecules and Cells, vol. 33, no. 3, pp. 223–228, 2012. View at Publisher · View at Google Scholar
  11. Y. Zhao, M. Koebis, S. Suo, S. Ohno, and S. Ishiura, “Regulation of the alternative splicing of sarcoplasmic reticulum Ca2+-ATPase1 (SERCA1) by phorbol 12-myristate 13-acetate (PMA) via a PKC pathway,” Biochemical and Biophysical Research Communications, vol. 423, no. 2, pp. 212–217, 2012. View at Publisher · View at Google Scholar
  12. T. A. Cooper, “Alternative splicing regulation impacts heart development,” Cell, vol. 120, no. 1, pp. 1–2, 2005. View at Publisher · View at Google Scholar · View at Scopus
  13. E. Lara-Pezzi, A. Dopazo, and M. Manzanares, “Understanding cardiovascular disease: a journey through the genome (and what we found there),” Disease Models & Mechanisms, vol. 5, no. 4, pp. 434–443, 2012. View at Publisher · View at Google Scholar
  14. V. Y. Bogdanov, “Blood coagulation and alternative pre-mRNA splicing: an overview,” Current Molecular Medicine, vol. 6, no. 8, pp. 859–869, 2006. View at Publisher · View at Google Scholar · View at Scopus
  15. M. W. Medina and R. M. Krauss, “Alternative splicing in the regulation of cholesterol homeostasis,” Current Opinion in Lipidology, vol. 24, no. 2, pp. 147–152, 2013. View at Publisher · View at Google Scholar
  16. K. Endo-Umeda, S. Uno, K. Fujimori et al., “Differential expression and function of alternative splicing variants of human liver X receptor alpha,” Molecular Pharmacology, vol. 81, no. 6, pp. 800–810, 2012. View at Publisher · View at Google Scholar
  17. M. Manetti, S. Guiducci, L. Ibba-Manneschi, and M. Matucci-Cerinic, “Impaired angiogenesis in systemic sclerosis: the emerging role of the antiangiogenic VEGF(165)b splice variant,” Trends in Cardiovascular Medicine, vol. 21, no. 7, pp. 204–210, 2011. View at Publisher · View at Google Scholar
  18. X. Xu, D. Yang, J. H. Ding et al., “ASF/SF2-regulated CaMKIIδ alternative splicing temporally reprograms excitation-contraction coupling in cardiac muscle,” Cell, vol. 120, no. 1, pp. 59–72, 2005. View at Publisher · View at Google Scholar · View at Scopus
  19. O. Fedorov, K. Huber, A. Eisenreich et al., “Specific CLK inhibitors from a novel chemotype for regulation of alternative splicing,” Chemistry & Biology, vol. 18, no. 1, pp. 67–76, 2011. View at Publisher · View at Google Scholar
  20. S. W. Kong, Y. W. Hu, J. W. K. Ho et al., “Heart failure-associated changes in RNA splicing of sarcomere genes,” Circulation, vol. 3, no. 2, pp. 138–146, 2010. View at Publisher · View at Google Scholar · View at Scopus
  21. R. Burkhardt, E. E. Kenny, J. K. Lowe et al., “Common SNPs in HMGCR in micronesians and whites associated with LDL-cholesterol levels affect alternative splicing of exon13,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 28, no. 11, pp. 2078–2084, 2008. View at Publisher · View at Google Scholar · View at Scopus
  22. H. Zhu, H. M. Tucker, K. E. Grear et al., “A common polymorphism decreases low-density lipoprotein receptor exon 12 splicing efficiency and associates with increased cholesterol,” Human Molecular Genetics, vol. 16, no. 14, pp. 1765–1772, 2007. View at Publisher · View at Google Scholar · View at Scopus
  23. R. J. Schmidt, Y. Zhang, Y. Zhao et al., “A novel splicing variant of proprotein convertase subtilisin/kexin type 9,” DNA and Cell Biology, vol. 27, no. 4, pp. 183–189, 2008. View at Publisher · View at Google Scholar · View at Scopus
  24. G. Gil, J. R. Smith, J. L. Goldstein, and M. S. Brown, “Optional exon in the 5′-untranslated region of 3-hydroxy-3-methylglutaryl coenzyme A synthase gene: conserved sequence and splicing pattern in humans and hamsters,” Proceedings of the National Academy of Sciences of the United States of America, vol. 84, no. 7, pp. 1863–1866, 1987. View at Scopus
  25. S. M. Houten, J. Koster, G. J. Romeijn et al., “Organization of the mevalonate kinase (MVK) gene and identification of novel mutations causing mevalonic aciduria and hyperimmunoglobulinaemia D and periodic fever syndrome,” European Journal of Human Genetics, vol. 9, no. 4, pp. 253–259, 2001. View at Publisher · View at Google Scholar · View at Scopus
  26. D. Kaida, T. Schneider-Poetsch, and M. Yoshida, “Splicing in oncogenesis and tumor suppression,” Cancer Science, vol. 103, no. 9, pp. 1611–1616, 2012. View at Publisher · View at Google Scholar
  27. R. M. Hagen and M. R. Ladomery, “Role of splice variants in the metastatic progression of prostate cancer,” Biochemical Society Transactions, vol. 40, no. 4, pp. 870–874, 2012. View at Publisher · View at Google Scholar
  28. J. Sampath and L. M. Pelus, “Alternative splice variants of survivin as potential targets in cancer,” Current Drug Discovery Technologies, vol. 4, no. 3, pp. 174–191, 2007. View at Publisher · View at Google Scholar · View at Scopus
  29. K. Miura, W. Fujibuchi, and I. Sasaki, “Alternative pre-mRNA splicing in digestive tract malignancy,” Cancer Science, vol. 102, no. 2, pp. 309–316, 2011. View at Publisher · View at Google Scholar · View at Scopus
  30. N. Okumura, H. Yoshida, Y. Kitagishi, Y. Nishimura, and S. Matsuda, “Alternative splicings on p53, BRCA1 and PTEN genes involved in breast cancer,” Biochemical and Biophysical Research Communications, vol. 413, no. 3, pp. 395–399, 2011. View at Publisher · View at Google Scholar
  31. M. Talieri, M. Devetzi, A. Scorilas et al., “Human kallikrein-related peptidase 12 (KLK12) splice variants expression in breast cancer and their clinical impact,” Tumor Biology, vol. 33, no. 4, pp. 1075–1084, 2012. View at Publisher · View at Google Scholar
  32. C. Tammaro, M. Raponi, D. I. Wilson, and D. Baralle, “BRCA1 exon 11 alternative splicing, multiple functions and the association with cancer,” Biochemical Society Transactions, vol. 40, no. 4, pp. 768–772, 2012. View at Publisher · View at Google Scholar
  33. J. Zhong, R. X. Cao, X. Y. Zu et al., “Identification and characterization of novel spliced variants of PRMT2 in breast carcinoma,” FEBS Journal, vol. 279, no. 2, pp. 316–335, 2012. View at Publisher · View at Google Scholar
  34. H. Albert, S. Santos, E. Battaglia, M. Brito, C. Monteiro, and D. Bagrel, “Differential expression of CDC25 phosphatases splice variants in human breast cancer cells,” Clinical Chemistry and Laboratory Medicine, vol. 49, no. 10, pp. 1707–1714, 2011.
  35. S. Sebban, R. Golan-Gerstl, R. Karni, O. Vaksman, B. Davidson, and R. Reich, “Alternatively spliced lysyl oxidase-like 4 isoforms have a pro-metastatic role in cancer,” Clinical and Experimental Metastasis, vol. 30, no. 1, pp. 103–117, 2013. View at Publisher · View at Google Scholar
  36. Y. Wang, D. W. Chan, V. W. S. Liu, P. M. Chiu, and H. Y. S. Ngan, “Differential functions of growth factor receptor-bound protein 7 (GRB7) and its variant GRB7v in ovarian carcinogenesis,” Clinical Cancer Research, vol. 16, no. 9, pp. 2529–2539, 2010. View at Publisher · View at Google Scholar · View at Scopus
  37. S. Haile and M. D. Sadar, “Androgen receptor and its splice variants in prostate cancer,” Cellular and Molecular Life Sciences, vol. 68, no. 24, pp. 3971–3981, 2011. View at Publisher · View at Google Scholar
  38. P. A. Usher, A. M. Sieuwerts, A. Bartels et al., “Identification of alternatively spliced TIMP-1 mRNA in cancer cell lines and colon cancer tissue,” Molecular Oncology, vol. 1, no. 2, pp. 205–215, 2007. View at Publisher · View at Google Scholar · View at Scopus
  39. D. C. Gotley, J. Fawcett, M. D. Walsh, J. A. Reeder, D. L. Simmons, and T. M. Antalis, “Alternatively spliced variants of the cell adhesion molecule CD44 and tumour progression in colorectal cancer,” British Journal of Cancer, vol. 74, no. 3, pp. 342–351, 1996. View at Scopus
  40. R. Pio and L. M. Montuenga, “Alternative splicing in lung cancer,” Journal of Thoracic Oncology, vol. 4, no. 6, pp. 674–678, 2009. View at Publisher · View at Google Scholar · View at Scopus
  41. D. Moretti, B. Del Bello, E. Cosci, M. Biagioli, C. Miracco, and E. Maellaro, “Novel variants of muscle calpain 3 identified in human melanoma cells: cisplatin-induced changes in vitro and differential expression in melanocytic lesions,” Carcinogenesis, vol. 30, no. 6, pp. 960–967, 2009. View at Publisher · View at Google Scholar · View at Scopus
  42. N. Hanoun, C. Bureau, T. Diab et al., “The SV2 variant of KLF6 is down-regulated in hepatocellular carcinoma and displays anti-proliferative and pro-apoptotic functions,” Journal of Hepatology, vol. 53, no. 5, pp. 880–888, 2010. View at Publisher · View at Google Scholar · View at Scopus
  43. Q. Yi and L. Tang, “Alternative spliced variants as biomarkers of colorectal cancer,” Current Drug Metabolism, vol. 12, no. 10, pp. 966–974, 2011. View at Publisher · View at Google Scholar
  44. G. S. Omenn, A. K. Yocum, and R. Menon, “Alternative splice variants, a new class of protein cancer biomarker candidates: findings in pancreatic cancer and breast cancer with systems biology implications,” Disease Markers, vol. 28, no. 4, pp. 241–251, 2010. View at Publisher · View at Google Scholar · View at Scopus
  45. Y. Lee, E. R. Gamazon, E. Rebman et al., “Variants affecting exon skipping contribute to complex traits,” PLOS Genetics, vol. 8, no. 10, Article ID e1002998, 2012.
  46. H. Feng, Z. Qin, and X. Zhang, “Opportunities and methods for studying alternative splicing in cancer with RNA-Seq,” Cancer Letters, 2012. View at Publisher · View at Google Scholar
  47. G. Li, J. H. Bahn, J. H. Lee et al., “Identification of allele-specific alternative mRNA processing via transcriptome sequencing,” Nucleic Acids Research, vol. 40, no. 13, article e104, 2012.
  48. L. Xi, A. Feber, V. Gupta et al., “Whole genome exon arrays identify differential expression of alternatively spliced, cancer-related genes in lung cancer,” Nucleic Acids Research, vol. 36, no. 20, pp. 6535–6547, 2008. View at Publisher · View at Google Scholar · View at Scopus
  49. C. Ben-Dov, B. Hartmann, J. Lundgren, and J. Valcárcel, “Genome-wide analysis of alternative pre-mRNA splicing,” Journal of Biological Chemistry, vol. 283, no. 3, pp. 1229–1233, 2008. View at Publisher · View at Google Scholar · View at Scopus
  50. O. Gautschi, D. Ratschiller, M. Gugger, D. C. Betticher, and J. Heighway, “Cyclin D1 in non-small cell lung cancer: a key driver of malignant transformation,” Lung Cancer, vol. 55, no. 1, pp. 1–14, 2007. View at Publisher · View at Google Scholar · View at Scopus
  51. G. Lamolle, M. Marin, and F. Alvarez-Valin, “Silent mutations in the gene encoding the p53 protein are preferentially located in conserved amino acid positions and splicing enhancers,” Mutation Research, vol. 600, no. 1-2, pp. 102–112, 2006. View at Publisher · View at Google Scholar · View at Scopus
  52. D. W. Neklason, C. H. Solomon, A. L. Dalton, S. K. Kuwada, and R. W. Burt, “Intron 4 mutation in APC gene results in splice defect and attenuated FAP phenotype,” Familial Cancer, vol. 3, no. 1, pp. 35–40, 2004. View at Publisher · View at Google Scholar · View at Scopus
  53. M. Raponi, J. Kralovicova, E. Copson et al., “Prediction of single-nucleotide substitutions that result in exon skipping: identification of a splicing silencer in BRCA1 exon 6,” Human Mutation, vol. 32, no. 4, pp. 436–444, 2011. View at Publisher · View at Google Scholar · View at Scopus
  54. H. X. Liu, L. Cartegni, M. Q. Zhang, and A. R. Krainer, “A mechanism for exon skipping caused by nonsense or missense mutations in BRCA1 and other genes,” Nature Genetics, vol. 27, no. 1, pp. 55–58, 2001. View at Publisher · View at Google Scholar · View at Scopus
  55. G. Narla, A. DiFeo, H. L. Reeves et al., “A germline DNA polymorphism enhances alternative splicing of the KLF6 tumor suppressor gene and is associated with increased prostate cancer risk,” Cancer Research, vol. 65, no. 4, pp. 1213–1222, 2005. View at Publisher · View at Google Scholar · View at Scopus
  56. G. Narla, A. Difeo, S. Yao et al., “Targeted inhibition of the KLF6 splice variant, KLF6 SV1, suppresses prostate cancer cell growth and spread,” Cancer Research, vol. 65, no. 13, pp. 5761–5768, 2005. View at Publisher · View at Google Scholar · View at Scopus
  57. A. DiFeo, L. Feld, E. Rodriguez et al., “A functional role for KLF6-SV1 in lung adenocarcinoma prognosis and chemotherapy response,” Cancer Research, vol. 68, no. 4, pp. 965–970, 2008. View at Publisher · View at Google Scholar · View at Scopus
  58. J. O. Yang, W. Y. Kim, and J. Bhak, “ssSNPTarget: genome-wide splice-site single nucleotide polymorphism database,” Human Mutation, vol. 30, no. 12, pp. E1010–E1020, 2009. View at Publisher · View at Google Scholar · View at Scopus
  59. A. G. Douglas and M. J. Wood, “RNA splicing: disease and therapy,” Briefings in Functional Genomics, vol. 10, no. 3, pp. 151–164, 2011. View at Publisher · View at Google Scholar
  60. R. K. Singh and T. A. Cooper, “Pre-mRNA splicing in disease and therapeutics,” Trends in Molecular Medicine, vol. 18, no. 8, pp. 472–482, 2012. View at Publisher · View at Google Scholar
  61. P. Spitali and A. Aartsma-Rus, “Splice modulating therapies for human disease,” Cell, vol. 148, no. 6, pp. 1085–1088, 2012. View at Publisher · View at Google Scholar
  62. K. Miura, W. Fujibuchi, and M. Unno, “Splice isoforms as therapeutic targets for colorectal cancer,” Carcinogenesis, vol. 33, no. 12, pp. 2311–2319, 2012. View at Publisher · View at Google Scholar
  63. J. P. Maciejewski and R. A. Padgett, “Defects in spliceosomal machinery: a new pathway of leukaemogenesis,” British Journal of Haematology, vol. 158, no. 2, pp. 165–173, 2012. View at Publisher · View at Google Scholar
  64. M. Hagiwara, “Alternative splicing: a new drug target of the post-genome era,” Biochimica et Biophysica Acta, vol. 1754, no. 1-2, pp. 324–331, 2005. View at Publisher · View at Google Scholar · View at Scopus
  65. C. A. Blair and X. Zi, “Potential molecular targeting of splice variants for cancer treatment,” Indian Journal of Experimental Biology, vol. 49, no. 11, pp. 836–839, 2011.
  66. R. J. Van Alphen, E. A. C. Wiemer, H. Burger, and F. A. L. M. Eskens, “The spliceosome as target for anticancer treatment,” British Journal of Cancer, vol. 100, no. 2, pp. 228–232, 2009. View at Publisher · View at Google Scholar · View at Scopus
  67. S. Bonnal, L. Vigevani, and J. Valcarcel, “The spliceosome as a target of novel antitumour drugs,” Nature Reviews Drug Discovery, vol. 11, no. 11, pp. 847–859, 2012. View at Publisher · View at Google Scholar
  68. E. S. Barrie, R. M. Smith, J. C. Sanford, and W. Sadee, “mRNA transcript diversity creates new opportunities for pharmacological intervention,” Molecular Pharmacology, vol. 81, no. 5, pp. 620–630, 2012. View at Publisher · View at Google Scholar
  69. M. L. Zhang, C. L. Lorson, E. J. Androphy, and J. Zhou, “An in vivo reporter system for measuring increased inclusion of exon 7 in SMN2 mRNA: potential therapy of SMA,” Gene Therapy, vol. 8, no. 20, pp. 1532–1538, 2001. View at Publisher · View at Google Scholar · View at Scopus
  70. C. Andreassi, J. Jarecki, J. Zhou et al., “Aclarubicin treatment restores SMN levels to cells derived from type I spinal muscular atrophy patients,” Human Molecular Genetics, vol. 10, no. 24, pp. 2841–2849, 2001. View at Scopus
  71. M. R. Lunn, D. E. Root, A. M. Martino et al., “Indoprofen upregulates the survival motor neuron protein through a cyclooxygenase-independent mechanism,” Chemistry and Biology, vol. 11, no. 11, pp. 1489–1493, 2004. View at Publisher · View at Google Scholar · View at Scopus
  72. C. Xu, X. Chen, S. M. Grzeschik, M. Ganta, and C. H. Wang, “Hydroxyurea enhances SMN2 gene expression through nitric oxide release,” Neurogenetics, vol. 12, no. 1, pp. 19–24, 2011. View at Publisher · View at Google Scholar · View at Scopus
  73. C. C. Weihl, A. M. Connolly, and A. Pestronk, “Valproate may improve strength and function in patients with type III/IV spinal muscle atrophy,” Neurology, vol. 67, no. 3, pp. 500–501, 2006. View at Publisher · View at Google Scholar · View at Scopus
  74. C. Y. Yuo, H. H. Lin, Y. S. Chang, W. K. Yang, and J. G. Chang, “5-(N-ethyl-N-isopropyl)-amiloride enhances SMN2 exon 7 inclusion and protein expression in spinal muscular atrophy cells,” Annals of Neurology, vol. 63, no. 1, pp. 26–34, 2008. View at Publisher · View at Google Scholar · View at Scopus
  75. C. Andreassi, C. Angelozzi, F. D. Tiziano et al., “Phenylbutyrate increases SMN expression in vitro: relevance for treatment of spinal muscular atrophy,” European Journal of Human Genetics, vol. 12, no. 1, pp. 59–65, 2004. View at Publisher · View at Google Scholar · View at Scopus
  76. Z. Zhang, O. Kelemen, M. A. Van Santen et al., “Synthesis and characterization of pseudocantharidins, novel phosphatase modulators that promote the inclusion of exon 7 into the SMN (survival of motoneuron) pre-mRNA,” Journal of Biological Chemistry, vol. 286, no. 12, pp. 10126–10136, 2011. View at Publisher · View at Google Scholar · View at Scopus
  77. I. S. K. Harahap, T. Saito, L. P. San et al., “Valproic acid increases SMN2 expression and modulates SF2/ASF and hnRNPA1 expression in SMA fibroblast cell lines,” Brain and Development, 2011. View at Publisher · View at Google Scholar · View at Scopus
  78. S. Zheng, Y. Chen, C. P. Donahue, M. S. Wolfe, and G. Varani, “Structural Basis for Stabilization of the Tau Pre-mRNA Splicing Regulatory Element by Novantrone (Mitoxantrone),” Chemistry and Biology, vol. 16, no. 5, pp. 557–566, 2009. View at Publisher · View at Google Scholar · View at Scopus
  79. J. S. Lewis and V. C. Jordan, “Selective estrogen receptor modulators (SERMs): mechanisms of anticarcinogenesis and drug resistance,” Mutation Research, vol. 591, no. 1-2, pp. 247–263, 2005. View at Publisher · View at Google Scholar · View at Scopus
  80. S. L. Lin, L. Y. Yan, X. T. Zhang et al., “ER-α36, a variant of ER-α, promotes tamoxifen agonist action in endometrial cancer cells via the MAPK/ERK and PI3K/Akt pathways,” PLoS ONE, vol. 5, no. 2, Article ID e9013, 2010. View at Publisher · View at Google Scholar · View at Scopus
  81. E. Zaharieva, J. K. Chipman, and M. Soller, “Alternative splicing interference by xenobiotics,” Toxicology, vol. 296, pp. 1–12, 2012. View at Publisher · View at Google Scholar
  82. D. Kaida, H. Motoyoshi, E. Tashiro et al., “Spliceostatin A targets SF3b and inhibits both splicing and nuclear retention of pre-mRNA,” Nature Chemical Biology, vol. 3, no. 9, pp. 576–583, 2007. View at Publisher · View at Google Scholar · View at Scopus
  83. Y. Kotake, K. Sagane, T. Owa et al., “Splicing factor SF3b as a target of the antitumor natural product pladienolide,” Nature Chemical Biology, vol. 3, no. 9, pp. 570–575, 2007. View at Publisher · View at Google Scholar · View at Scopus
  84. L. Fan, C. Lagisetti, C. C. Edwards, T. R. Webb, and P. M. Potter, “Sudemycins, novel small molecule analogues of FR901464, induce alternative gene splicing,” ACS Chemical Biology, vol. 6, no. 6, pp. 582–589, 2011. View at Publisher · View at Google Scholar · View at Scopus
  85. A. Corrionero, B. Miñana, and J. Valcárcel, “Reduced fidelity of branch point recognition and alternative splicing induced by the anti-tumor drug spliceostatin A,” Genes and Development, vol. 25, no. 5, pp. 445–459, 2011. View at Publisher · View at Google Scholar · View at Scopus
  86. R. Furumai, K. Uchida, Y. Komi et al., “Spliceostatin A blocks angiogenesis by inhibiting global gene expression including VEGF,” Cancer Science, vol. 101, no. 11, pp. 2483–2489, 2010. View at Publisher · View at Google Scholar · View at Scopus
  87. H. Nakajima, B. Sato, T. Fujita, S. Takase, H. Terano, and M. Okuhara, “New antitumor substances, FR901463, FR901464 and FR901465: I. Taxonomy, fermentation, isolation, physico-chemical properties and biological activities,” Journal of Antibiotics, vol. 49, no. 12, pp. 1196–1203, 1996. View at Scopus
  88. B. J. Albert, P. A. McPherson, K. O'Brien et al., “Meayamycin inhibits pre-messenger RNA splicing and exhibits picomolar activity against multidrug-resistant cells,” Molecular Cancer Therapeutics, vol. 8, no. 8, pp. 2308–2318, 2009. View at Publisher · View at Google Scholar · View at Scopus
  89. J. Woolard, W. Vousden, S. J. Moss et al., “Borrelidin modulates the alternative splicing of VEGF in favour of anti-angiogenic isoforms,” Chemical Science, vol. 2011, no. 2, pp. 273–278, 2011.
  90. U. Shamim, S. Hanif, A. Albanyan et al., “Resveratrol-induced apoptosis is enhanced in low pH environments associated with cancer,” Journal of Cellular Physiology, vol. 227, no. 4, pp. 1493–1500, 2012. View at Publisher · View at Google Scholar
  91. J. Jakubikova, D. Cervi, M. Ooi et al., “Anti-tumor activity and signaling events triggered by the isothiocyanates, sulforaphane and phenethyl isothiocyanate, in multiple myeloma,” Haematologica, vol. 96, no. 8, pp. 1170–1179, 2011. View at Publisher · View at Google Scholar
  92. M. A. Markus, F. Z. Marques, and B. J. Morris, “Resveratrol, by modulating RNA processing factor levels, can influence the alternative splicing of pre-mRNAs,” PLoS One, vol. 6, no. 12, Article ID e28926, 2011.
  93. K. Miura, W. Fujibuchi, and M. Unno, “Splice variants in apoptotic pathway,” Experimental Oncology, vol. 34, no. 3, pp. 212–217, 2012.
  94. C. Schwerk and K. Schulze-Osthoff, “Regulation of apoptosis by alternative pre-mRNA splicing,” Molecular Cell, vol. 19, no. 1, pp. 1–13, 2005. View at Publisher · View at Google Scholar · View at Scopus
  95. L. Shkreta, U. Froehlich, E. R. Paquet, J. Toutant, S. A. Elela, and B. Chabot, “Anticancer drugs affect the alternative splicing of Bcl-x and other human apoptotic genes,” Molecular Cancer Therapeutics, vol. 7, no. 6, pp. 1398–1409, 2008. View at Publisher · View at Google Scholar · View at Scopus
  96. J. Lee, J. Zhou, X. Zheng et al., “Identification of a novel cis-element that regulates alternative splicing of Bcl-x pre-mRNA,” Biochemical and Biophysical Research Communications, vol. 420, no. 2, pp. 467–472, 2012. View at Publisher · View at Google Scholar
  97. 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
  98. J. C. Shultz, R. W. Goehe, D. S. Wijesinghe et al., “Alternative splicing of caspase 9 is modulated by the phosphoinositide 3-kinase/Akt pathway via phosphorylation of SRp30a,” Cancer Research, vol. 70, no. 22, pp. 9185–9196, 2010. View at Publisher · View at Google Scholar · View at Scopus
  99. C. Puppin, N. Passon, A. Franzoni, D. Russo, and G. Damante, “Histone deacetylase inhibitors control the transcription and alternative splicing of prohibitin in thyroid tumor cells,” Oncology Reports, vol. 25, no. 2, pp. 393–397, 2011. View at Publisher · View at Google Scholar · View at Scopus
  100. S. Wu, C. Li, W. Huang, W. Li, and R. W. Li, “Alternative splicing regulated by butyrate in bovine epithelial cells,” PLoS One, vol. 7, no. 6, Article ID e39182, 2012.
  101. C. Lee and Q. Wang, “Bioinformatics analysis of alternative splicing,” Briefings in Bioinformatics, vol. 6, no. 1, pp. 23–33, 2005. View at Publisher · View at Google Scholar · View at Scopus
  102. L. D. Florea, “Bioinformatics of alternative splicing and its regulation,” Briefings in Bioinformatics, vol. 7, no. 1, pp. 55–69, 2006. View at Publisher · View at Google Scholar · View at Scopus
  103. N. Kim and C. Lee, “Bioinformatics detection of alternative splicing,” Methods in Molecular Biology, vol. 452, pp. 179–197, 2008. View at Publisher · View at Google Scholar · View at Scopus
  104. H. Ji, Q. Zhou, F. Wen, H. Xia, X. Lu, and Y. Li, “AsMamDB: an alternative splice database of mammals,” Nucleic Acids Research, vol. 29, no. 1, pp. 260–263, 2001. View at Scopus
  105. Y. H. Huang, Y. T. Chen, J. J. Lai, S. T. Yang, and U. C. Yang, “PALS db: putative alternative splicing database,” Nucleic Acids Research, vol. 30, no. 1, pp. 186–190, 2002. View at Scopus
  106. C. Lee, L. Atanelov, B. Modrek, and Y. Xing, “ASAP: the alternative splicing annotation project,” Nucleic Acids Research, vol. 31, no. 1, pp. 101–105, 2003. View at Publisher · View at Google Scholar · View at Scopus
  107. H. Pospisil, A. Herrmann, R. H. Bortfeldt, and J. G. Reich, “EASED: Extended Alternatively Spliced EST Database,” Nucleic Acids Research, vol. 32, pp. D70–D74, 2004. View at Scopus
  108. F. R. Hsu, H. Y. Chang, Y. L. Lin et al., “AVATAR: a database for genome-wide alternative splicing event detection using large scale ESTs and mRNAs,” , Bioinformation, vol. 1, no. 1, pp. 16–18, 2005. View at Publisher · View at Google Scholar
  109. C. L. Zheng, Y. S. Kwon, L. I. Hai-Ri et al., “MAASE: an alternative splicing database designed for supporting splicing microarray applications,” RNA, vol. 11, no. 12, pp. 1767–1776, 2005. View at Publisher · View at Google Scholar · View at Scopus
  110. H. Zhang, J. Hu, M. Recce, and B. Tian, “PolyA_DB: a database for mammalian mRNA polyadenylation,” Nucleic Acids Research, vol. 33, pp. D116–D120, 2005. View at Publisher · View at Google Scholar · View at Scopus
  111. V. Le Texier, J. J. Riethoven, V. Kumanduri et al., “AltTrans: transcript pattern variants annotated for both alternative splicing and alternative polyadenylation,” BMC Bioinformatics, vol. 7, article 169, 2006. View at Publisher · View at Google Scholar · View at Scopus
  112. R. Kostadinov, N. Malhotra, M. Viotti, R. Shine, L. D'Antonio, and P. Bagga, “GRSDB: a database of quadruplex forming G-rich sequences in alternatively processed mammalian pre-mRNA sequences,” Nucleic Acids Research, vol. 34, pp. D119–124, 2006. View at Scopus
  113. D. Holste, G. Huo, V. Tung, and C. B. Burge, “HOLLYWOOD: a comparative relational database of alternative splicing,” Nucleic Acids Research, vol. 34, pp. D56–62, 2006. View at Scopus
  114. S. Stamm, J. J. Riethoven, V. Le Texier et al., “ASD: a bioinformatics resource on alternative splicing,” Nucleic Acids Research, vol. 34, pp. D46–55, 2006. View at Scopus
  115. D. Rambaldi, B. Felice, V. Praz, P. Bucher, D. Cittaro, and A. Guffanti, “Splicy: a web-based tool for the prediction of possible alternative splicing events from Affymetrix probeset data,” BMC Bioinformatics, vol. 8, no. 1, article no. S17, 2007. View at Publisher · View at Google Scholar · View at Scopus
  116. S. Foissac and M. Sammeth, “ASTALAVISTA: dynamic and flexible analysis of alternative splicing events in custom gene datasets,” Nucleic Acids Research, vol. 35, pp. W297–299, 2007. View at Publisher · View at Google Scholar · View at Scopus
  117. Z. Lacroix, C. Legendre, L. Raschid, and B. Snyder, “BIPASS: BioInformatics Pipeline Alternative Splicing Services,” Nucleic Acids Research, vol. 35, pp. W292–296, 2007. View at Publisher · View at Google Scholar · View at Scopus
  118. Y. Lee, Y. Lee, B. Kim et al., “ECgene: an alternative splicing database update,” Nucleic Acids Research, vol. 35, no. 1, pp. D99–D103, 2007. View at Publisher · View at Google Scholar · View at Scopus
  119. A. Bhasi, R. V. Pandey, S. P. Utharasamy, and P. Senapathy, “EuSplice: a unified resource for the analysis of splice signals and alternative splicing in eukaryotic genes,” Bioinformatics, vol. 23, no. 14, pp. 1815–1823, 2007. View at Publisher · View at Google Scholar · View at Scopus
  120. M. C. Ryan, B. R. Zeeberg, N. J. Caplen et al., “SpliceCenter: a suite of web-based bioinformatic applications for evaluating the impact of alternative splicing on RT-PCR, RNAi, microarray, and peptide-based studies,” BMC Bioinformatics, vol. 9, article 313, 2008. View at Publisher · View at Google Scholar · View at Scopus
  121. T. Castrignanò, M. D'Antonio, A. Anselmo et al., “ASPicDB: a database resource for alternative splicing analysis,” Bioinformatics, vol. 24, no. 10, pp. 1300–1304, 2008. View at Publisher · View at Google Scholar · View at Scopus
  122. J. M. Bechtel, P. Rajesh, I. Ilikchyan et al., “The Alternative Splicing Mutation Database: a hub for investigations of alternative splicing using mutational evidence,” BMC Research Notes, vol. 1, article 3, 2008. View at Publisher · View at Google Scholar · View at Scopus
  123. F. Birzele, R. Küffner, F. Meier, F. Oefinger, C. Potthast, and R. Zimmer, “ProSAS: a database for analyzing alternative splicing in the context of protein structures,” Nucleic Acids Research, vol. 36, no. 1, pp. D63–D68, 2008. View at Publisher · View at Google Scholar · View at Scopus
  124. M. Floris, M. Orsini, and T. A. Thanaraj, “Splice-mediated variants of proteins (SpliVaP)—data and characterization of changes in signatures among protein isoforms due to alternative splicing,” BMC Genomics, vol. 9, article 453, 2008. View at Publisher · View at Google Scholar · View at Scopus
  125. A. Bhasi, P. Philip, V. T. Sreedharan, and P. Senapathy, “AspAlt: a tool for inter-database, inter-genomic and user-specific comparative analysis of alternative transcription and alternative splicing in 46 eukaryotes,” Genomics, vol. 94, no. 1, pp. 48–54, 2009. View at Publisher · View at Google Scholar · View at Scopus
  126. G. Koscielny, V. L. Texier, C. Gopalakrishnan et al., “ASTD: the Alternative Splicing and Transcript Diversity database,” Genomics, vol. 93, no. 3, pp. 213–220, 2009. View at Publisher · View at Google Scholar · View at Scopus
  127. R. Sinha, T. Lenser, N. Jahn et al., “TassDB2: a comprehensive database of subtle alternative splicing events,” BMC Bioinformatics, vol. 11, article 216, 2010. View at Publisher · View at Google Scholar · View at Scopus
  128. J. I. Takeda, Y. Suzuki, R. Sakate et al., “H-DBAS: Human-transcriptome database for alternative splicing: update 2010,” Nucleic Acids Research, vol. 38, no. 1, Article ID gkp984, pp. D86–D90, 2009. View at Publisher · View at Google Scholar · View at Scopus
  129. J. E. Kroll, P. A. Galante, D. T. Ohara, F. C. Navarro, L. Ohno-Machado, and S. J. de Souza, “SPLOOCE: a new portal for the analysis of human splicing variants,” RNA Biology, vol. 9, no. 11, pp. 1339–1343, 2012.
  130. J. M. Rodriguez, P. Maietta, I. Ezkurdia et al., “APPRIS: annotation of principal and alternative splice isoforms,” Nucleic Acids Research, vol. 41, pp. 110–117, 2013. View at Publisher · View at Google Scholar
  131. F. Piva, M. Giulietti, A. B. Burini, and G. Principato, “SpliceAid 2: a database of human splicing factors expression data and RNA target motifs,” Human Mutation, vol. 33, no. 1, pp. 81–85, 2012. View at Publisher · View at Google Scholar
  132. E. Wingender, T. Schoeps, and J. Donitz, “TFClass: an expandable hierarchical classification of human transcription factors,” Nucleic Acids Research, vol. 41, pp. 165–170, 2013. View at Publisher · View at Google Scholar