Skip to main content
American Journal of Human Genetics logoLink to American Journal of Human Genetics
. 1997 Aug;61(2):259–266. doi: 10.1086/514856

The regulation of splice-site selection, and its role in human disease.

T A Cooper 1, W Mattox 1
PMCID: PMC1715899  PMID: 9311728

Full text

PDF
259

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Amrein H., Hedley M. L., Maniatis T. The role of specific protein-RNA and protein-protein interactions in positive and negative control of pre-mRNA splicing by Transformer 2. Cell. 1994 Feb 25;76(4):735–746. doi: 10.1016/0092-8674(94)90512-6. [DOI] [PubMed] [Google Scholar]
  2. Antic D., Keene J. D. Embryonic lethal abnormal visual RNA-binding proteins involved in growth, differentiation, and posttranscriptional gene expression. Am J Hum Genet. 1997 Aug;61(2):273–278. doi: 10.1086/514866. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Aruffo A., Stamenkovic I., Melnick M., Underhill C. B., Seed B. CD44 is the principal cell surface receptor for hyaluronate. Cell. 1990 Jun 29;61(7):1303–1313. doi: 10.1016/0092-8674(90)90694-a. [DOI] [PubMed] [Google Scholar]
  4. Berget S. M. Exon recognition in vertebrate splicing. J Biol Chem. 1995 Feb 10;270(6):2411–2414. doi: 10.1074/jbc.270.6.2411. [DOI] [PubMed] [Google Scholar]
  5. Black D. L. Activation of c-src neuron-specific splicing by an unusual RNA element in vivo and in vitro. Cell. 1992 May 29;69(5):795–807. doi: 10.1016/0092-8674(92)90291-j. [DOI] [PubMed] [Google Scholar]
  6. Boggs R. T., Gregor P., Idriss S., Belote J. M., McKeown M. Regulation of sexual differentiation in D. melanogaster via alternative splicing of RNA from the transformer gene. Cell. 1987 Aug 28;50(5):739–747. doi: 10.1016/0092-8674(87)90332-1. [DOI] [PubMed] [Google Scholar]
  7. Caputi M., Casari G., Guenzi S., Tagliabue R., Sidoli A., Melo C. A., Baralle F. E. A novel bipartite splicing enhancer modulates the differential processing of the human fibronectin EDA exon. Nucleic Acids Res. 1994 Mar 25;22(6):1018–1022. doi: 10.1093/nar/22.6.1018. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Chelly J., Gilgenkrantz H., Lambert M., Hamard G., Chafey P., Récan D., Katz P., de la Chapelle A., Koenig M., Ginjaar I. B. Effect of dystrophin gene deletions on mRNA levels and processing in Duchenne and Becker muscular dystrophies. Cell. 1990 Dec 21;63(6):1239–1248. doi: 10.1016/0092-8674(90)90419-f. [DOI] [PubMed] [Google Scholar]
  9. Cooper D. L., Dougherty G. J. To metastasize or not? Selection of CD44 splice sites. Nat Med. 1995 Jul;1(7):635–637. doi: 10.1038/nm0795-635. [DOI] [PubMed] [Google Scholar]
  10. Coulter L. R., Landree M. A., Cooper T. A. Identification of a new class of exonic splicing enhancers by in vivo selection. Mol Cell Biol. 1997 Apr;17(4):2143–2150. doi: 10.1128/mcb.17.4.2143. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Das S., Levinson B., Whitney S., Vulpe C., Packman S., Gitschier J. Diverse mutations in patients with Menkes disease often lead to exon skipping. Am J Hum Genet. 1994 Nov;55(5):883–889. [PMC free article] [PubMed] [Google Scholar]
  12. De Meirleir L., Lissens W., Benelli C., Ponsot G., Desguerre I., Marsac C., Rodriguez D., Saudubray J. M., Poggi F., Liebaers I. Aberrant splicing of exon 6 in the pyruvate dehydrogenase-E1 alpha mRNA linked to a silent mutation in a large family with Leigh's encephalomyelopathy. Pediatr Res. 1994 Dec;36(6):707–712. doi: 10.1203/00006450-199412000-00004. [DOI] [PubMed] [Google Scholar]
  13. Denhez F., Lafyatis R. Conservation of regulated alternative splicing and identification of functional domains in vertebrate homologs to the Drosophila splicing regulator, suppressor-of-white-apricot. J Biol Chem. 1994 Jun 10;269(23):16170–16179. [PubMed] [Google Scholar]
  14. Dirksen W. P., Hampson R. K., Sun Q., Rottman F. M. A purine-rich exon sequence enhances alternative splicing of bovine growth hormone pre-mRNA. J Biol Chem. 1994 Mar 4;269(9):6431–6436. [PubMed] [Google Scholar]
  15. Fu X. D. The superfamily of arginine/serine-rich splicing factors. RNA. 1995 Sep;1(7):663–680. [PMC free article] [PubMed] [Google Scholar]
  16. Gooding C., Roberts G. C., Moreau G., Nadal-Ginard B., Smith C. W. Smooth muscle-specific switching of alpha-tropomyosin mutually exclusive exon selection by specific inhibition of the strong default exon. EMBO J. 1994 Aug 15;13(16):3861–3872. doi: 10.1002/j.1460-2075.1994.tb06697.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Guo W., Mulligan G. J., Wormsley S., Helfman D. M. Alternative splicing of beta-tropomyosin pre-mRNA: cis-acting elements and cellular factors that block the use of a skeletal muscle exon in nonmuscle cells. Genes Dev. 1991 Nov;5(11):2096–2107. doi: 10.1101/gad.5.11.2096. [DOI] [PubMed] [Google Scholar]
  18. Hampson R. K., La Follette L., Rottman F. M. Alternative processing of bovine growth hormone mRNA is influenced by downstream exon sequences. Mol Cell Biol. 1989 Apr;9(4):1604–1610. doi: 10.1128/mcb.9.4.1604. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Hasegawa Y., Kawame H., Ida H., Ohashi T., Eto Y. Single exon mutation in arylsulfatase A gene has two effects: loss of enzyme activity and aberrant splicing. Hum Genet. 1994 Apr;93(4):415–420. doi: 10.1007/BF00201666. [DOI] [PubMed] [Google Scholar]
  20. Heinrichs V., Baker B. S. The Drosophila SR protein RBP1 contributes to the regulation of doublesex alternative splicing by recognizing RBP1 RNA target sequences. EMBO J. 1995 Aug 15;14(16):3987–4000. doi: 10.1002/j.1460-2075.1995.tb00070.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Hoffman E. P., Morgan J. E., Watkins S. C., Partridge T. A. Somatic reversion/suppression of the mouse mdx phenotype in vivo. J Neurol Sci. 1990 Oct;99(1):9–25. doi: 10.1016/0022-510x(90)90195-s. [DOI] [PubMed] [Google Scholar]
  22. Huh G. S., Hynes R. O. Regulation of alternative pre-mRNA splicing by a novel repeated hexanucleotide element. Genes Dev. 1994 Jul 1;8(13):1561–1574. doi: 10.1101/gad.8.13.1561. [DOI] [PubMed] [Google Scholar]
  23. Humphrey M. B., Bryan J., Cooper T. A., Berget S. M. A 32-nucleotide exon-splicing enhancer regulates usage of competing 5' splice sites in a differential internal exon. Mol Cell Biol. 1995 Aug;15(8):3979–3988. doi: 10.1128/mcb.15.8.3979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Inoue K., Hoshijima K., Higuchi I., Sakamoto H., Shimura Y. Binding of the Drosophila transformer and transformer-2 proteins to the regulatory elements of doublesex primary transcript for sex-specific RNA processing. Proc Natl Acad Sci U S A. 1992 Sep 1;89(17):8092–8096. doi: 10.1073/pnas.89.17.8092. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Jin Y., Dietz H. C., Montgomery R. A., Bell W. R., McIntosh I., Coller B., Bray P. F. Glanzmann thrombasthenia. Cooperation between sequence variants in cis during splice site selection. J Clin Invest. 1996 Oct 15;98(8):1745–1754. doi: 10.1172/JCI118973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Klein C. J., Coovert D. D., Bulman D. E., Ray P. N., Mendell J. R., Burghes A. H. Somatic reversion/suppression in Duchenne muscular dystrophy (DMD): evidence supporting a frame-restoring mechanism in rare dystrophin-positive fibers. Am J Hum Genet. 1992 May;50(5):950–959. [PMC free article] [PubMed] [Google Scholar]
  27. Koenig M., Beggs A. H., Moyer M., Scherpf S., Heindrich K., Bettecken T., Meng G., Müller C. R., Lindlöf M., Kaariainen H. The molecular basis for Duchenne versus Becker muscular dystrophy: correlation of severity with type of deletion. Am J Hum Genet. 1989 Oct;45(4):498–506. [PMC free article] [PubMed] [Google Scholar]
  28. Krawczak M., Reiss J., Cooper D. N. The mutational spectrum of single base-pair substitutions in mRNA splice junctions of human genes: causes and consequences. Hum Genet. 1992 Sep-Oct;90(1-2):41–54. doi: 10.1007/BF00210743. [DOI] [PubMed] [Google Scholar]
  29. Lavigueur A., La Branche H., Kornblihtt A. R., Chabot B. A splicing enhancer in the human fibronectin alternate ED1 exon interacts with SR proteins and stimulates U2 snRNP binding. Genes Dev. 1993 Dec;7(12A):2405–2417. doi: 10.1101/gad.7.12a.2405. [DOI] [PubMed] [Google Scholar]
  30. Ligtenberg M. J., Gennissen A. M., Vos H. L., Hilkens J. A single nucleotide polymorphism in an exon dictates allele dependent differential splicing of episialin mRNA. Nucleic Acids Res. 1991 Jan 25;19(2):297–301. doi: 10.1093/nar/19.2.297. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Llewellyn D. H., Scobie G. A., Urquhart A. J., Whatley S. D., Roberts A. G., Harrison P. R., Elder G. H. Acute intermittent porphyria caused by defective splicing of porphobilinogen deaminase RNA: a synonymous codon mutation at -22 bp from the 5' splice site causes skipping of exon 3. J Med Genet. 1996 May;33(5):437–438. doi: 10.1136/jmg.33.5.437. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Lynch K. W., Maniatis T. Synergistic interactions between two distinct elements of a regulated splicing enhancer. Genes Dev. 1995 Feb 1;9(3):284–293. doi: 10.1101/gad.9.3.284. [DOI] [PubMed] [Google Scholar]
  33. Malhotra S. B., Hart K. A., Klamut H. J., Thomas N. S., Bodrug S. E., Burghes A. H., Bobrow M., Harper P. S., Thompson M. W., Ray P. N. Frame-shift deletions in patients with Duchenne and Becker muscular dystrophy. Science. 1988 Nov 4;242(4879):755–759. doi: 10.1126/science.3055295. [DOI] [PubMed] [Google Scholar]
  34. Manley J. L., Tacke R. SR proteins and splicing control. Genes Dev. 1996 Jul 1;10(13):1569–1579. doi: 10.1101/gad.10.13.1569. [DOI] [PubMed] [Google Scholar]
  35. Maquat L. E. When cells stop making sense: effects of nonsense codons on RNA metabolism in vertebrate cells. RNA. 1995 Jul;1(5):453–465. [PMC free article] [PubMed] [Google Scholar]
  36. McKeown M. Alternative mRNA splicing. Annu Rev Cell Biol. 1992;8:133–155. doi: 10.1146/annurev.cb.08.110192.001025. [DOI] [PubMed] [Google Scholar]
  37. Merzak A., Koocheckpour S., Pilkington G. J. CD44 mediates human glioma cell adhesion and invasion in vitro. Cancer Res. 1994 Aug 1;54(15):3988–3992. [PubMed] [Google Scholar]
  38. Mochizuki H., Nishi T., Bruner J. M., Lee P. S., Levin V. A., Saya H. Alternative splicing of neurofibromatosis type 1 gene transcript in malignant brain tumors: PCR analysis of frozen-section mRNA. Mol Carcinog. 1992;6(2):83–87. doi: 10.1002/mc.2940060203. [DOI] [PubMed] [Google Scholar]
  39. Oyama F., Hirohashi S., Sakamoto M., Titani K., Sekiguchi K. Coordinate oncodevelopmental modulation of alternative splicing of fibronectin pre-messenger RNA at ED-A, ED-B, and CS1 regions in human liver tumors. Cancer Res. 1993 May 1;53(9):2005–2011. [PubMed] [Google Scholar]
  40. Padgett R. A., Grabowski P. J., Konarska M. M., Seiler S., Sharp P. A. Splicing of messenger RNA precursors. Annu Rev Biochem. 1986;55:1119–1150. doi: 10.1146/annurev.bi.55.070186.005351. [DOI] [PubMed] [Google Scholar]
  41. Ploos van Amstel J. K., Bergman A. J., van Beurden E. A., Roijers J. F., Peelen T., van den Berg I. E., Poll-The B. T., Kvittingen E. A., Berger R. Hereditary tyrosinemia type 1: novel missense, nonsense and splice consensus mutations in the human fumarylacetoacetate hydrolase gene; variability of the genotype-phenotype relationship. Hum Genet. 1996 Jan;97(1):51–59. doi: 10.1007/BF00218833. [DOI] [PubMed] [Google Scholar]
  42. Ramchatesingh J., Zahler A. M., Neugebauer K. M., Roth M. B., Cooper T. A. A subset of SR proteins activates splicing of the cardiac troponin T alternative exon by direct interactions with an exonic enhancer. Mol Cell Biol. 1995 Sep;15(9):4898–4907. doi: 10.1128/mcb.15.9.4898. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Reed R. Initial splice-site recognition and pairing during pre-mRNA splicing. Curr Opin Genet Dev. 1996 Apr;6(2):215–220. doi: 10.1016/s0959-437x(96)80053-0. [DOI] [PubMed] [Google Scholar]
  44. Reed R., Maniatis T. A role for exon sequences and splice-site proximity in splice-site selection. Cell. 1986 Aug 29;46(5):681–690. doi: 10.1016/0092-8674(86)90343-0. [DOI] [PubMed] [Google Scholar]
  45. Roth M. B., Murphy C., Gall J. G. A monoclonal antibody that recognizes a phosphorylated epitope stains lampbrush chromosome loops and small granules in the amphibian germinal vesicle. J Cell Biol. 1990 Dec;111(6 Pt 1):2217–2223. doi: 10.1083/jcb.111.6.2217. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Ryan K. J., Cooper T. A. Muscle-specific splicing enhancers regulate inclusion of the cardiac troponin T alternative exon in embryonic skeletal muscle. Mol Cell Biol. 1996 Aug;16(8):4014–4023. doi: 10.1128/mcb.16.8.4014. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Salmi M., Grön-Virta K., Sointu P., Grenman R., Kalimo H., Jalkanen S. Regulated expression of exon v6 containing isoforms of CD44 in man: downregulation during malignant transformation of tumors of squamocellular origin. J Cell Biol. 1993 Jul;122(2):431–442. doi: 10.1083/jcb.122.2.431. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Santisteban I., Arredondo-Vega F. X., Kelly S., Loubser M., Meydan N., Roifman C., Howell P. L., Bowen T., Weinberg K. I., Schroeder M. L. Three new adenosine deaminase mutations that define a splicing enhancer and cause severe and partial phenotypes: implications for evolution of a CpG hotspot and expression of a transduced ADA cDNA. Hum Mol Genet. 1995 Nov;4(11):2081–2087. doi: 10.1093/hmg/4.11.2081. [DOI] [PubMed] [Google Scholar]
  49. Sarkissian M., Winne A., Lafyatis R. The mammalian homolog of suppressor-of-white-apricot regulates alternative mRNA splicing of CD45 exon 4 and fibronectin IIICS. J Biol Chem. 1996 Dec 6;271(49):31106–31114. doi: 10.1074/jbc.271.49.31106. [DOI] [PubMed] [Google Scholar]
  50. Screaton G. R., Cáceres J. F., Mayeda A., Bell M. V., Plebanski M., Jackson D. G., Bell J. I., Krainer A. R. Identification and characterization of three members of the human SR family of pre-mRNA splicing factors. EMBO J. 1995 Sep 1;14(17):4336–4349. doi: 10.1002/j.1460-2075.1995.tb00108.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Seiter S., Arch R., Reber S., Komitowski D., Hofmann M., Ponta H., Herrlich P., Matzku S., Zöller M. Prevention of tumor metastasis formation by anti-variant CD44. J Exp Med. 1993 Feb 1;177(2):443–455. doi: 10.1084/jem.177.2.443. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Sherratt T. G., Vulliamy T., Dubowitz V., Sewry C. A., Strong P. N. Exon skipping and translation in patients with frameshift deletions in the dystrophin gene. Am J Hum Genet. 1993 Nov;53(5):1007–1015. [PMC free article] [PubMed] [Google Scholar]
  53. Sierakowska H., Sambade M. J., Agrawal S., Kole R. Repair of thalassemic human beta-globin mRNA in mammalian cells by antisense oligonucleotides. Proc Natl Acad Sci U S A. 1996 Nov 12;93(23):12840–12844. doi: 10.1073/pnas.93.23.12840. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Spikes D. A., Kramer J., Bingham P. M., Van Doren K. SWAP pre-mRNA splicing regulators are a novel, ancient protein family sharing a highly conserved sequence motif with the prp21 family of constitutive splicing proteins. Nucleic Acids Res. 1994 Oct 25;22(21):4510–4519. doi: 10.1093/nar/22.21.4510. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Steingrimsdottir H., Rowley G., Dorado G., Cole J., Lehmann A. R. Mutations which alter splicing in the human hypoxanthine-guanine phosphoribosyltransferase gene. Nucleic Acids Res. 1992 Mar 25;20(6):1201–1208. doi: 10.1093/nar/20.6.1201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Tacke R., Goridis C. Alternative splicing in the neural cell adhesion molecule pre-mRNA: regulation of exon 18 skipping depends on the 5'-splice site. Genes Dev. 1991 Aug;5(8):1416–1429. doi: 10.1101/gad.5.8.1416. [DOI] [PubMed] [Google Scholar]
  57. Takagaki Y., Seipelt R. L., Peterson M. L., Manley J. L. The polyadenylation factor CstF-64 regulates alternative processing of IgM heavy chain pre-mRNA during B cell differentiation. Cell. 1996 Nov 29;87(5):941–952. doi: 10.1016/s0092-8674(00)82000-0. [DOI] [PubMed] [Google Scholar]
  58. Tanabe K. K., Ellis L. M., Saya H. Expression of CD44R1 adhesion molecule in colon carcinomas and metastases. Lancet. 1993 Mar 20;341(8847):725–726. doi: 10.1016/0140-6736(93)90490-8. [DOI] [PubMed] [Google Scholar]
  59. Tanaka K., Watakabe A., Shimura Y. Polypurine sequences within a downstream exon function as a splicing enhancer. Mol Cell Biol. 1994 Feb;14(2):1347–1354. doi: 10.1128/mcb.14.2.1347. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Tian H., Kole R. Selection of novel exon recognition elements from a pool of random sequences. Mol Cell Biol. 1995 Nov;15(11):6291–6298. doi: 10.1128/mcb.15.11.6291. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Tian M., Maniatis T. A splicing enhancer complex controls alternative splicing of doublesex pre-mRNA. Cell. 1993 Jul 16;74(1):105–114. doi: 10.1016/0092-8674(93)90298-5. [DOI] [PubMed] [Google Scholar]
  62. Tuerk C., Gold L. Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase. Science. 1990 Aug 3;249(4968):505–510. doi: 10.1126/science.2200121. [DOI] [PubMed] [Google Scholar]
  63. Wakamatsu N., Kobayashi H., Miyatake T., Tsuji S. A novel exon mutation in the human beta-hexosaminidase beta subunit gene affects 3' splice site selection. J Biol Chem. 1992 Feb 5;267(4):2406–2413. [PubMed] [Google Scholar]
  64. Wang Z., Hoffmann H. M., Grabowski P. J. Intrinsic U2AF binding is modulated by exon enhancer signals in parallel with changes in splicing activity. RNA. 1995 Mar;1(1):21–35. [PMC free article] [PubMed] [Google Scholar]
  65. Watakabe A., Tanaka K., Shimura Y. The role of exon sequences in splice site selection. Genes Dev. 1993 Mar;7(3):407–418. doi: 10.1101/gad.7.3.407. [DOI] [PubMed] [Google Scholar]
  66. Xu R., Teng J., Cooper T. A. The cardiac troponin T alternative exon contains a novel purine-rich positive splicing element. Mol Cell Biol. 1993 Jun;13(6):3660–3674. doi: 10.1128/mcb.13.6.3660. [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. Yeakley J. M., Morfin J. P., Rosenfeld M. G., Fu X. D. A complex of nuclear proteins mediates SR protein binding to a purine-rich splicing enhancer. Proc Natl Acad Sci U S A. 1996 Jul 23;93(15):7582–7587. doi: 10.1073/pnas.93.15.7582. [DOI] [PMC free article] [PubMed] [Google Scholar]
  68. Zachar Z., Chou T. B., Bingham P. M. Evidence that a regulatory gene autoregulates splicing of its transcript. EMBO J. 1987 Dec 20;6(13):4105–4111. doi: 10.1002/j.1460-2075.1987.tb02756.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  69. Zahler A. M., Neugebauer K. M., Lane W. S., Roth M. B. Distinct functions of SR proteins in alternative pre-mRNA splicing. Science. 1993 Apr 9;260(5105):219–222. doi: 10.1126/science.8385799. [DOI] [PubMed] [Google Scholar]
  70. van Oers C. C., Adema G. J., Zandberg H., Moen T. C., Baas P. D. Two different sequence elements within exon 4 are necessary for calcitonin-specific splicing of the human calcitonin/calcitonin gene-related peptide I pre-mRNA. Mol Cell Biol. 1994 Feb;14(2):951–960. doi: 10.1128/mcb.14.2.951. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from American Journal of Human Genetics are provided here courtesy of American Society of Human Genetics

RESOURCES