PSF Suppresses Tau Exon 10 Inclusion by Interacting with a Stem-Loop Structure Downstream of Exon 10

  • Payal Ray
  • Amar Kar
  • Kazuo Fushimi
  • Necat Havlioglu
  • Xiaoping Chen
  • Jane Y. Wu
Article

Abstract

Microtubule binding protein Tau has been implicated in a wide range of neurodegenerative disorders collectively classified as tauopathies. Exon 10 of the human tau gene, which codes for a microtubule binding repeat region, is alternatively spliced to form Tau protein isoforms containing either four or three microtubule binding repeats, Tau4R and Tau3R, respectively. The levels of different Tau splicing isoforms are fine-tuned by alternative splicing with the ratio of Tau4R/Tau3R maintained approximately at one in adult neurons. Mutations that disrupt tau exon 10 splicing regulation cause an imbalance of different tau splicing isoforms and have been associated with tauopathy. To search for factors interacting with tau pre-messenger RNA (pre-mRNA) and regulating tau exon 10 alternative splicing, we performed a yeast RNA–protein interaction screen and identified polypyrimidine tract binding protein associated splicing factor (PSF) as a candidate tau exon 10 splicing regulator. UV crosslinking experiments show that PSF binds to the stem-loop structure at the 5′ splice site downstream of tau exon 10. This PSF-interacting RNA element is distinct from known PSF binding sites previously identified in other genes. Overexpression of PSF promotes tau exon 10 exclusion, whereas down-regulation of the endogenous PSF facilitates exon 10 inclusion. Immunostaining shows that PSF is expressed in the human brain regions affected by tauopathy. Our data reveal a new player in tau exon 10 alternative splicing regulation and uncover a previously unknown mechanism of PSF in regulating tau pre-mRNA splicing.

Keywords

Tau Alternative splicing regulation Tauopathy RNA stem-loop secondary structure Polypyrimidine tract binding protein associated splicing factor (PSF) 

References

  1. Akhmedov AT, Lopez BS (2000) Human 100-kDa homologous DNA-pairing protein is the splicing factor PSF and promotes DNA strand invasion. Nucleic Acids Res 28(16):3022–3030PubMedCrossRefGoogle Scholar
  2. Andreadis A (2005) Tau gene alternative splicing: expression patterns, regulation and modulation of function in normal brain and neurodegenerative diseases. Biochim Biophys Acta 1739(2–3):91–103PubMedGoogle Scholar
  3. Andreadis A (2006) Misregulation of tau alternative splicing in neurodegeneration and dementia. Prog Mol Subcell Biol 44:89–107PubMedCrossRefGoogle Scholar
  4. Andreadis A, Brown WM, Kosik KS (1992) Structure and novel exons of the human tau gene. Biochemistry 31(43):10626–10633PubMedCrossRefGoogle Scholar
  5. Antunes-Martins A, Mizuno K, Irvine EE, Lepicard EM, Giese KP (2007) Sex-dependent up-regulation of two splicing factors, Psf and Srp20, during hippocampal memory formation. Learn Mem 14:693–702PubMedCrossRefGoogle Scholar
  6. Black D (2000) Protein diversity from alternative splicing: a challenge for bioinformatics and post-genome biology. Cell 103(3):367–370PubMedCrossRefGoogle Scholar
  7. Blanchette M, Chabot B (1997) A highly stable duplex structure sequesters the 5′ splice site region of hnRNP A1 alternative exon 7B. RNA 3(4):405–419PubMedGoogle Scholar
  8. Boeve BF, Hutton M (2008) Refining frontotemporal dementia with parkinsonism linked to chromosome 17: introducing FTDP-17 (MAPT) and FTDP-17 (PGRN). Arch Neurol 65(4):460–464PubMedCrossRefGoogle Scholar
  9. Broderick J, Wang J, Andreadis A (2004) Heterogeneous nuclear ribonucleoprotein E2 binds to tau exon 10 and moderately activates its splicing. Gene 331:107–114PubMedCrossRefGoogle Scholar
  10. Buratti E, Baralle FE (2004) Influence of RNA secondary structure on the pre-mRNA splicing process. Mol Cell Biol 24(24):10505–10514PubMedCrossRefGoogle Scholar
  11. Buxade M, Morrice N, Krebs DL, Proud CG (2008) The PSF.p54nrb complex is a novel Mnk substrate that binds the mRNA for tumor necrosis factor alpha. J Biol Chem 283(1):57–65PubMedCrossRefGoogle Scholar
  12. Cairns NJ, Bigio EH, Mackenzie IR, Neumann M, Lee VM, Hatanpaa KJ, White CL 3rd, Schneider JA, Grinberg LT, Halliday G, Duyckaerts C, Lowe JS, Holm IE, Tolnay M, Okamoto K, Yokoo H, Murayama S, Woulfe J, Munoz DG, Dickson DW, Ince PG, Trojanowski JQ, Mann DM (2007) Consortium for frontotemporal lobar degeneration. Neuropathologic diagnostic and nosologic criteria for frontotemporal lobar degeneration: consensus of the consortium for frontotemporal lobar degeneration. Acta Neuropathol 114(1):5–22PubMedCrossRefGoogle Scholar
  13. Chanas-Sacre G, Mazy-Servais C, Wattiez R, Pirard S, Rogister B, Patton JG, Belachew S, Malgrange B, Moonen G, Leprince P (1999) Identification of PSF, the polypyrimidine tract-binding protein-associated splicing factor, as a developmentally regulated neuronal protein. J Neurosci Res 57(1):62–73PubMedCrossRefGoogle Scholar
  14. Clouet d’Orval B, d’Aubenton Carafa Y, Sirand-Pugnet P, Gallego M, Brody E, Marie J (1991) RNA secondary structure repression of a muscle-specific exon in HeLa cell nuclear extracts. Science 252(5014):1823–1828PubMedCrossRefGoogle Scholar
  15. Cobbold LC, Spriggs KA, Haines SJ, Dobbyn HC, Hayes C, de Moor CH, Lilley KS, Bushell M, Willis AE (2008) Identification of internal ribosome entry segment (IRES)-trans-acting factors for the Myc family of IRESs. Mol Cell Biol 28(1):40–49PubMedCrossRefGoogle Scholar
  16. Collet J, Fehrat L, Pollard H, Ribas de Pouplana L, Charton G, Bernard A, Moreau J, Ben-Ari Y, Khrestchatisky M (1997) Developmentally regulated alternative splicing of mRNAs encoding N-terminal tau variants in the rat hippocampus: structural and functional implications. Eur J Neurosci 9:2723–2733PubMedCrossRefGoogle Scholar
  17. Colombo R, Tavian D, Baker MC, Richardson AM, Snowden JS, Neary D, Mann DM, Pickering-Brown SM (2009) Recent origin and spread of a common Welsh MAPT splice mutation causing frontotemporal lobar degeneration. Neurogenetics 10(4):313–318PubMedCrossRefGoogle Scholar
  18. Connell JW, Gibb GM, Betts JC, Blackstock WP, Gallo J, Lovestone S, Hutton M, Anderton BH (2001) Effects of FTDP-17 mutations on the in vitro phosphorylation of tau by glycogen synthase kinase 3beta identified by mass spectrometry demonstrate certain mutations exert long-range conformational changes. FEBS Lett 493:40–44PubMedCrossRefGoogle Scholar
  19. Cooper TA, Wan L, Dreyfuss G (2009) RNA and disease. Cell 136(4):777–793PubMedCrossRefGoogle Scholar
  20. Dawson HN, Cantillana V, Chen L, Vitek MP (2007) The tau N279K exon 10 splicing mutation recapitulates frontotemporal dementia and parkinsonism linked to chromosome 17 tauopathy in a mouse model. J Neurosci 27(34):9155–9168PubMedCrossRefGoogle Scholar
  21. Donahue CP, Muratore C, Wu JY, Kosik KS, Wolfe MS (2006) Stabilization of the tau exon 10 stem loop alters pre-mRNA splicing. J Biol Chem 281(33):23302–23306PubMedCrossRefGoogle Scholar
  22. D’Souza I, Schellenberg GD (2000) Determinants of 4-repeat tau expression. Coordination between enhancing and inhibitory splicing sequences for exon 10 inclusion. J Biol Chem 275(23):17700–17709PubMedCrossRefGoogle Scholar
  23. Duong HA, Robles MS, Knutti D, Weitz CJ (2011) A molecular mechanism for circadian clock negative feedback. Science 332(6036):1436–1439PubMedCrossRefGoogle Scholar
  24. Eperon LP, IR Graham, AD Griffiths and IC Eperon (1988) Effects of RNA secondary structure on alternative splicing of pre-mRNA: is folding limited to a region behind the transcribing RNA polymerase? Cell 54:393–401Google Scholar
  25. Gao QS, Memmott J, Lafyatis R, Stamm S, Screaton G, Andreadis A (2000) Complex regulation of tau exon 10, whose missplicing causes frontotemporal dementia. J Neurochem 74(2):490–500PubMedCrossRefGoogle Scholar
  26. Gao L, Wang J, Wang Y, Andreadis A (2007) SR protein 9G8 modulates splicing of tau exon 10 via its proximal downstream intron, a clustering region for frontotemporal dementia mutations. Mol Cell Neurosci 34(1):48–58PubMedCrossRefGoogle Scholar
  27. Glatz DC, Rujescu D, Tang Y, Berendt FJ, Hartmann AM, Faltraco F, Rosenberg C, Hulette C, Jellinger K, Hampel H, Riederer P, Moller HJ, Andreadis A, Henkel K, Stamm S (2006) The alternative splicing of tau exon 10 and its regulatory proteins CLK2 and TRA2-BETA1 changes in sporadic Alzheimer’s disease. J Neurochem 96(3):635–644PubMedCrossRefGoogle Scholar
  28. Goedert M, Jakes R (1990) Expression of separate isoforms of human tau protein: correlation with the tau pattern in brain and effects on tubulin polymerization. EMBO J 9(13):4225–4230PubMedGoogle Scholar
  29. Goedert M, Jakes R (2005) Mutations causing neurodegenerative tauopathies. Biochim Biophys Acta 1739(2–3):240–250PubMedGoogle Scholar
  30. Goedert M, Spillantini MG (2001) Tau gene mutations and neurodegeneration. Biochem Soc Symp (67):59–71Google Scholar
  31. Goedert M, Spillantini MG, Jakes R, Rutherford D, Crowther RA (1989a) Multiple isoforms of human microtubule-associated protein tau: sequences and localization in neurofibrillary tangles of Alzheimer’s disease. Neuron 3(4):519–526PubMedCrossRefGoogle Scholar
  32. Goedert M, Spillantini MG, Potier MC, Ulrich J, Crowther RA (1989b) Cloning and sequencing of the cDNA encoding an isoform of microtubule-associated protein tau containing four tandem repeats: differential expression of tau protein mRNAs in human brain. EMBO J 8(2):393–399PubMedGoogle Scholar
  33. Goode BL, Chau M, Denis PE, Feinstein SC (2000) Structural and functional differences between 3-repeat and 4-repeat tau isoforms. Implications for normal tau function and the onset of neurodegenetative disease. J Biol Chem 275:38182–38189PubMedCrossRefGoogle Scholar
  34. Gozani O, Patton JG, Reed R (1994) A novel set of spliceosome-associated proteins and the essential splicing factor PSF bind stably to pre-mRNA prior to catalytic step II of the splicing reaction. EMBO J 13(14):3356–3367PubMedGoogle Scholar
  35. Grant RC, Harwood SJ, Wells RD (1968) The synthesis and characterization of poly d (I-C) poly d (I-C). J Am Chem Soc 90(16):4474–4476Google Scholar
  36. Greco-Stewart VS, Thibault CS, Pelchat M (2006) Binding of the polypyrimidine tract-binding protein-associated splicing factor (PSF) to the hepatitis delta virus RNA. Virology 356(1–2):35–44PubMedCrossRefGoogle Scholar
  37. Grover A, Houlden H, Baker M, Adamson J, Lewis J, Prihar G, Pickering-Brown S, Duff K, Hutton M (1999) 5′ Splice site mutations in tau associated with the inherited dementia FTDP-17 affect a stem-loop structure that regulates alternative splicing of exon 10. J Biol Chem 274(21):15134–15143PubMedCrossRefGoogle Scholar
  38. Hartmann M, Rujescu D, Giannakouros T, Nikolakaki E, Goedert M, Mandelkow EM, Gao QS, Andreadis A, Stamm S (2001) Regulation of alternative splicing of human tau exon 10 by phosphorylation of splicing factors. Mol Cell Neurosci 18(1):80–90PubMedCrossRefGoogle Scholar
  39. Hasegawa M, Smith MJ, Goedert M (1998) Tau proteins with FTDP-17 mutations have a reduced ability to promote microtubule assembly. FEBS Lett 437:207–210PubMedCrossRefGoogle Scholar
  40. Hasegawa M, Smith MJ, Iijima M, Tabira T, Goedert M (1999) FTDP-17 mutations N279K and S305N in tau produce increased splicing of exon 10. FEBS Lett 443:93–96PubMedCrossRefGoogle Scholar
  41. Himmler A (1989) Structure of the bovine tau gene: alternatively spliced transcripts generate a protein family. Mol Cell Biol 9:1389–1396PubMedGoogle Scholar
  42. Hutton M, Lendon CL, Rizzu P, Baker M, Froelich S, Houlden H, Pickering-Brown S, Chakraverty S, Isaacs A, Grover A, Hackett J, Adamson J, Lincoln S, Dickson D, Davies P, Petersen RC, Stevens M, de Graaff E, Wauters E, van Baren J, Hillebrand M, Joosse M, Kwon JM, Nowotny P, Che LK, Norton J, Morris JC, Reed LA, Trojanowski J, Basun H, Lannfelt L, Neystat M, Fahn S, Dark F, Tannenberg T, Dodd PR, Hayward N, Kwok JB, Schofield PR, Andreadis A, Snowden J, Craufurd D, Neary D, Owen F, Oostra BA, Hardy J, Goate A, van Swieten J, Mann D, Lynch T, Heutink P (1998) Association of missense and 5′-splice-site mutations in tau with the inherited dementia FTDP-17. Nature 393(6686):702–705PubMedCrossRefGoogle Scholar
  43. Iqbal K, Liu F, Gong CX, Alonso Adel C, Grundke-Iqbal I (2009) Mechanisms of tau-induced neurodegeneration. Acta Neuropathol 118(1):53–69PubMedCrossRefGoogle Scholar
  44. Iqbal K, F Liu, CX Gong, I Grundke-Iqbal (2010). Tau in Alzheimer Disease and related Tauopathies. Curr Alzheimer Res 7:656–664.Google Scholar
  45. Jiang ZH, Zhang WJ, Rao Y, Wu JY (1998) Regulation of Ich-1 pre-mRNA alternative splicing and apoptosis by mammalian splicing factors. Proc Natl Acad Sci USA 95(16):9155–9160PubMedCrossRefGoogle Scholar
  46. Jiang Z, Cote J, Kwon JM, Goate AM, Wu JY (2000) Aberrant splicing of tau pre-mRNA caused by intronic mutations associated with the inherited dementia frontotemporal dementia with parkinsonism linked to chromosome 17. Mol Cell Biol 20(11):4036–4048PubMedCrossRefGoogle Scholar
  47. Jiang Z, Tang H, Havlioglu N, Zhang X, Stamm S, Yan R, Wu JY (2003) Mutations in tau gene exon 10 associated with FTDP-17 alter the activity of an exonic splicing enhancer to interact with Tra2 beta. J Biol Chem 278(21):18997–19007PubMedCrossRefGoogle Scholar
  48. Kalbfuss B, Mason SA, Misteli T (2001) Correction of alternative splicing of tau in frontotemporal dementia and parkinsonism linked to chromosome 17. J Biol Chem 276(46):42986–42993PubMedCrossRefGoogle Scholar
  49. Kameoka S, Duque P, Konarska MM (2004) P54(nrb) associates with the 5′ splice site within large transcription/splicing complexes. EMBO J 23(8):1782–1791PubMedCrossRefGoogle Scholar
  50. Kaneko S, Rozenblatt-Rosen O, Meyerson M, Manley JL (2007) The multifunctional protein p54nrb/PSF recruits the exonuclease XRN2 to facilitate pre-mRNA 3′ processing and transcription termination. Genes Dev 21(14):1779–1789PubMedCrossRefGoogle Scholar
  51. Kar A, Kuo D, He R, Zhou J, Wu JY (2005) Tau alternative splicing and frontotemporal dementia. Alzheimer Dis Assoc Disord 19(Suppl 1):S29–S36PubMedCrossRefGoogle Scholar
  52. Kar A, Havlioglu N, Tarn WY, Wu JY (2006) RBM4 interacts with an intronic element and stimulates tau exon 10 inclusion. J Biol Chem 281(34):24479–24488PubMedCrossRefGoogle Scholar
  53. Kar A, Fushimi K, Zhou Xh, Ray P, Shi C, Chen Xp, Liu Zr, Chen S, Wu JY (2011) RNA Helicase p68 (DDX5) regulates tau exon 10 splicing by modulating a stem-loop structure at the 5′ splice site. Mol Cell Biol 31:1812–1821PubMedCrossRefGoogle Scholar
  54. Kondo S, Yamamoto N, Murakami T, Okumura M, Mayeda A, Imaizumi K (2004) Tra2 beta, SF2/ASF and SRp30c modulate the function of an exonic splicing enhancer in exon 10 of tau pre-mRNA. Genes Cells 9:121–130PubMedCrossRefGoogle Scholar
  55. Konzack S, Thies E, Marx A, Mandelkow EM, Mandelkow E (2007) Swimming against the tide: mobility of the microtubule-associated protein tau in neurons. J Neurosci 27:9916–9927PubMedCrossRefGoogle Scholar
  56. Krawczak M, Reiss J, Cooper DN (1992) The mutational spectrum of single base-pair substitutions in mRNA splice junctions of human genes: causes and consequences. Hum Genet 90(1–2):41–54PubMedGoogle Scholar
  57. LeBoeuf AC, Levy SF, Gaylord M, Bhattacharya A, Singh AK, Jordan MA, Wilson L, Feinstein SC (2008) FTDP-17 mutations in Tau alter the regulation of microtubule dynamics: an "alternative core" model for normal and pathological Tau action. J Biol Chem 283:36406–36415PubMedCrossRefGoogle Scholar
  58. Lee G, Neve RL, Kosik KS (1989) The microtubule binding domain of tau protein. Neuron 2:1615–1624PubMedCrossRefGoogle Scholar
  59. Lee VM, Goedert M, Trojanowski JQ (2001) Neurodegenerative tauopathies. Annu Rev Neurosci 24:1121–1159PubMedCrossRefGoogle Scholar
  60. Libri D, Piseri A, Fiszman MY (1991) Tissue-specific splicing in vivo of the beta-tropomyosin gene: dependence on an RNA secondary structure. Science 252(5014):1842–1845PubMedCrossRefGoogle Scholar
  61. Lichtenberg-Kraag B, Mandelkow EM (1990) Isoforms of tau protein from mammalian brain and avian erythrocytes: structure, self-assembly, and elasticity. J Struct Biol 105:46–53PubMedCrossRefGoogle Scholar
  62. Liu F, Gong CX (2008) Tau exon 10 alternative splicing and tauopathies. Mol Neurodegener 3:8PubMedCrossRefGoogle Scholar
  63. Lowery LA, Rubin J, Sive H (2007) Whitesnake/sfpq is required for cell survival and neuronal development in the zebrafish. Dev Dyn 236(5):1347–1357PubMedCrossRefGoogle Scholar
  64. Mackenzie IR, Rademakers R (2007) The molecular genetics and neuropathology of frontotemporal lobar degeneration: recent developments. Neurogenet Nov 8(4):237–248CrossRefGoogle Scholar
  65. Mackenzie IR, Neumann M, Bigio EH, Cairns NJ, Alafuzoff I, Kril J, Kovacs GG, Ghetti B, Halliday G, Holm IE, Ince PG, Kamphorst W, Revesz T, Rozemuller AJ, Kumar-Singh S, Akiyama H, Baborie A, Spina S, Dickson DW, Trojanowski JQ, Mann DM (2010) Nomenclature and nosology for neuropathologic subtypes of frontotemporal lobar degeneration: an update. Acta Neuropathol 119(1):1–4PubMedCrossRefGoogle Scholar
  66. Mathur M, Tucker PW, Samuels HH (2001) PSF is a novel corepressor that mediates its effect through Sin3A and the DNA binding domain of nuclear hormone receptors. Mol Cell Biol 21(7):2298–2311PubMedCrossRefGoogle Scholar
  67. Matlin AJ, Clark F, Smith CW (2005) Understanding alternative splicing: towards a cellular code. Nat Rev Mol Cell Biol 6:386–398PubMedCrossRefGoogle Scholar
  68. Matsuo M, Nishio H, Kitoh Y, Francke U, Nakamura H (1992) Partial deletion of a dystrophin gene leads to exon skipping and to loss of an intra-exon hairpin structure from the predicted mRNA precursor. Biochem Biophys Res Commun 182(2):495–500PubMedCrossRefGoogle Scholar
  69. Medeiros R, Baglietto-Vargas D, Laferla FM (2010) The role of tau in Alzheimer’s disease and related disorders. CNS Neurosci Ther. doi:10.1111/j.1755-5949.2010.00177.x
  70. Melton AA, Jackson J, Wang J, Lynch KW (2007) Combinatorial control of signal-induced exon repression by hnRNP L and PSF. Mol Cell Biol 27(19):6972–6984PubMedCrossRefGoogle Scholar
  71. Mercken M, Fischer I, Kosik KS, Nixon RA (1995) Three distinct axonal transport rates for tau, tubulin, and microtubule-associated proteins: evidence for dynamic interactions of tau with microtubules in vivo. J Neurosci 15(12):8259–8267PubMedGoogle Scholar
  72. Montejo de Garcini E, Corrochano L, Wischik CM, Diaz Nido J, Correas I, Avila J (1992) Differentiation of neuroblastoma cells correlates with an altered splicing pattern of tau RNA. FEBS Lett 299:10–14PubMedCrossRefGoogle Scholar
  73. Morfini GA, Burns M, Binder LI, Kanaan NM, LaPointe N, Bosco DA, Brown RH Jr, Brown H, Tiwari A, Hayward L, Edgar J, Nave KA, Garberrn J, Atagi Y, Song Y, Pigino G, Brady ST (2009) Axonal transport defects in neurodegenerative diseases. J Neurosci 29(41):12776–12786PubMedCrossRefGoogle Scholar
  74. Neumann M, Tolnay M, Mackenzie IR (2009) The molecular basis of frontotemporal dementia. Expert Rev Mol Med 11:e23PubMedCrossRefGoogle Scholar
  75. Neve RL, Harris P, Kosik KS, Kurnit DM, Donlon TA (1986) Identification of cDNA clones for the human microtubule-associated protein tau and chromosomal localization of the genes for tau and microtubule-associated protein 2. Brain Res 387(3):271–280PubMedGoogle Scholar
  76. Nilsen TW, Graveley BR (2010) Expansion of the eukaryotic proteome by alternative splicing. Nature 463(7280):457–463PubMedCrossRefGoogle Scholar
  77. Panda D, Goode BL, Feinstein SC, Wilson L (1995) Kinetic stabilization of microtubule dynamics at steady state by tau and microtubule-binding domains of tau. Biochemistry 34(35):11117–11127PubMedCrossRefGoogle Scholar
  78. Patton JG, Porro EB, Galceran J, Tempst P, Nadal-Ginard B (1993) Cloning and characterization of PSF, a novel pre-mRNA splicing factor. Genes Dev 7(3):393–406PubMedCrossRefGoogle Scholar
  79. Peng R, Dye BT, Perez I, Barnard DC, Thompson AB, Patton JG (2002) PSF and p54nrb bind a conserved stem in U5 snRNA. RNA 8(10):1334–1347PubMedCrossRefGoogle Scholar
  80. Pickering-Brown S, Baker M, Yen SH, Liu WK, Hasegawa M, Cairns N, Lantos PL, Rossor M, Iwatsubo T, Davies Y, Allsop D, Furlong R, Owen F, Hardy J, Mann D, Hutton M (2000) Pick’s disease is associated with mutations in the tau gene. Ann Neurol 48(6):859–867PubMedCrossRefGoogle Scholar
  81. Pickering-Brown SM, Richardson AM, Snowden JS, McDonagh AM, Burns A, Braude W, Baker M, Liu WK, Yen SH, Hardy J, Hutton M, Davies Y, Allsop D, Craufurd D, Neary D, Mann DM (2002) Inherited frontotemporal dementia in nine British families associated with intronic mutations in the tau gene. Brain 125(Pt 4):732–751PubMedCrossRefGoogle Scholar
  82. Sewer MB, Nguyen VQ, Huang CJ, Tucker PW, Kagawa N, Waterman MR (2002) Transcriptional activation of human CYP17 in H295R adrenocortical cells depends on complex formation among p54(nrb)/NonO, protein-associated splicing factor, and SF-1, a complex that also participates in repression of transcription. Endocrinology 143(4):1280–1290PubMedCrossRefGoogle Scholar
  83. Shav-Tal Y, Zipori D (2002) PSF and p54(nrb)/NonO—multi-functional nuclear proteins. FEBS Lett 531(2):109–114PubMedCrossRefGoogle Scholar
  84. Singh NN, Singh RN, Androphy EJ (2007) Modulating role of RNA structure in alternative splicing of a critical exon in the spinal muscular atrophy genes. Nucleic Acids Res 35(2):371–389PubMedCrossRefGoogle Scholar
  85. Sirand-Pugnet P, Durosay P, Clouet d’Orval BC, Brody E, Marie J (1995) Beta-tropomyosin pre-mRNA folding around a muscle-specific exon interferes with several steps of spliceosome assembly. J Mol Biol 251(5):591–602PubMedCrossRefGoogle Scholar
  86. Solis AS, Shariat N, Patton JG (2008) Splicing fidelity, enhancers, and disease. Front Biosci 13:1926–1942PubMedCrossRefGoogle Scholar
  87. Spillantini MG, Murrell JR, Goedert M, Farlow MR, Klug A, Ghetti B (1998) Mutation in the tau gene in familial multiple system tauopathy with presenile dementia. Proc Natl Acad Sci USA 95:7737–7741PubMedCrossRefGoogle Scholar
  88. Spillantini MG, Van Swieten JC, Goedert M (2000) Tau gene mutations in frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). Neurogenetics 2(4):193–205PubMedGoogle Scholar
  89. Straub T, Grue P, Uhse A, Lisby M, Knudsen BR, Tange TO, Westergaard O, Boege F (1998) The RNA-splicing factor PSF/p54 controls DNA-topoisomerase I activity by a direct interaction. J Biol Chem 273(41):26261–26264PubMedCrossRefGoogle Scholar
  90. Tomoo K, Yao TM, Minoura K, Hiraoka S, Sumida M, Taniguchi T, Ishida T (2005) Possible role of each repeat structure of the microtubule-binding domain of the tau protein in in vitro aggregation. J Biochem 138:413–423PubMedCrossRefGoogle Scholar
  91. Urban RJ, Bodenburg Y, Kurosky A, Wood TG, Gasic S (2000) Polypyrimidine tract-binding protein-associated splicing factor is a negative regulator of transcriptional activity of the porcine p450scc insulin-like growth factor response element. Mol Endocrinol 14(6):774–782PubMedCrossRefGoogle Scholar
  92. Utton MA, Connell J, Asuni AA, van Slegtenhorst M, Hutton M, de Silva R, Lees AJ, Miller CC, Anderton BH (2002) The slow axonal transport of the microtubule-associated protein tau and the transport rates of different isoforms and mutants in cultured neurons. J Neurosci 22:6394–6400PubMedGoogle Scholar
  93. Varani L, Hasegawa M, Spillantini MG, Smith MJ, Murrell JR, Ghetti B, Klug A, Goedert M, Varani G (1999) Structure of tau exon 10 splicing regulatory element RNA and destabilization by mutations of frontotemporal dementia and parkinsonism linked to chromosome 17. Proc Natl Acad Sci USA 96:8229–8234PubMedCrossRefGoogle Scholar
  94. Varani L, Spillantini MG, Goedert M, Varani G (2000) Structural basis for recognition of the RNA major groove in the tau exon 10 splicing regulatory element by aminoglycoside antibiotics. Nucleic Acids Res 28:710–719PubMedCrossRefGoogle Scholar
  95. Wang GS, Cooper TA (2007) Splicing in disease: disruption of the splicing code and the decoding machinery. Nat Rev Genet 8(10):749–761PubMedCrossRefGoogle Scholar
  96. Wang J, Gao QS, Wang Y, Lafyatis R, Stamm S, Andreadis A (2004) Tau exon 10, whose missplicing causes frontotemporal dementia, is regulated by an intricate interplay of cis elements and trans factors. J Neurochem 88(5):1078–1090PubMedCrossRefGoogle Scholar
  97. Wang G, Cui Y, Zhang G, Garen A, Song X (2009) Regulation of proto-oncogene transcription, cell proliferation, and tumorigenesis in mice by PSF protein and a VL30 noncoding RNA. Proc Natl Acad Sci 106(39):16794–16798PubMedCrossRefGoogle Scholar
  98. Wang Y, Gao L, Tse SW, Andreadis A (2010) Heterogeneous nuclear ribonucleoprotein E3 modestly activates splicing of tau exon 10 via its proximal downstream intron, a hotspot for frontotemporal dementia mutations. Gene 451(1–2):23–31PubMedCrossRefGoogle Scholar
  99. Ward AJ, Cooper TA (2010) The pathobiology of splicing. J Pathol 220(2):152–163PubMedGoogle Scholar
  100. Wei ML, Andreadis A (1998) Splicing of a regulated exon reveals additional complexity in the axonal microtubule-associated protein tau. J Neurochem 70:1346–1356PubMedCrossRefGoogle Scholar
  101. Wei ML, Memmott J, Screaton G, Andreadis A (2000) The splicing determinants of a regulated exon in the axonal MAP tau reside within the exon and in its upstream intron. Brain Res Mol Brain Res 80(2):207–218PubMedCrossRefGoogle Scholar
  102. Wolfe MS (2009) Tau mutations in neurodegenerative diseases. J Biol Chem 284(10):6021–6025PubMedCrossRefGoogle Scholar
  103. Wu JY, Postashkin JA (2009) Alternative splicing in the nervous system. In: Squire LR (ed) Encyclopedia of neuroscience, vol 1. Academic/Elsevier, Oxford, pp 245–251CrossRefGoogle Scholar
  104. Wu JY, Yuan L, Havlioglu N (2004) Alternatively spliced genes. In: Meyers RA (ed) Encyclopedia of molecular cell biology and molecular medicine, vol 1, 2nd edn. Wiley-VCH, Chichester, 125–177Google Scholar
  105. Wu JY, Kar A, Kuo D, Yu B, Havlioglu N (2006) SRp54 (SFRS11), a regulator for tau exon 10 alternative splicing identified by an expression cloning strategy. Mol Cell Biol 26(18):6739–6747PubMedCrossRefGoogle Scholar
  106. Yang Z, Sui Y, Xiong S, Liour SS, Phillips AC, Ko L (2007) Switched alternative splicing of oncogene CoAA during embryonal carcinoma stem cell differentiation. Nucleic Acids Res 35(6):1919–1932PubMedCrossRefGoogle Scholar
  107. Yu Q, Guo J, Zhou J (2004) A minimal length between tau exon 10 and 11 is required for correct splicing of exon 10. J Neurochem 90(1):164–172PubMedCrossRefGoogle Scholar
  108. Zhang Z, Carmichael GG (2001) The fate of dsRNA in the nucleus: a p54(nrb)-containing complex mediates the nuclear retention of promiscuously A-to-I edited RNAs. Cell 106(4):465–475PubMedCrossRefGoogle Scholar
  109. Zhou J, Yu Q, Zou T (2008) Alternative splicing of exon 10 in the tau gene as a target for treatment of tauopathies. BMC Neurosci 9(Suppl 2):S10PubMedCrossRefGoogle Scholar
  110. Zychlinski D, Erkelenz S et al (2009) Limited complementarity between U1 snRNA and a retroviral 5′ splice site permits its attenuation via RNA secondary structure. Nucleic Acids Res 37(22):7429–7440PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Payal Ray
    • 1
  • Amar Kar
    • 1
  • Kazuo Fushimi
    • 1
  • Necat Havlioglu
    • 2
  • Xiaoping Chen
    • 1
  • Jane Y. Wu
    • 1
  1. 1.Department of Neurology, Lurie Cancer Center, Center for Genetic MedicineNorthwestern University Feinberg School of MedicineChicagoUSA
  2. 2.Department of PathologySaint Louis UniversitySt. LouisUSA

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