Skip to main content
SpringerLink
Log in

Phosphorylation-Dependent Control of the Pre-mRNA Splicing Machinery

  • Chapter
Book cover Regulation of Alternative Splicing

Part of the book series: Progress in Molecular and Subcellular Biology ((PMSB,volume 31))

Abstract

In this chapter, experiments will be reviewed which lead from the initial hypothesis of the role of protein phosphorylation in pre-mRNA splicing to the elucidation of mechanism(s) by which this modification alters the function of splicing factors. Phosphorylation has been implicated in the assembly of the spliceosome (Tazi et al. 1992; Mermoud et al. 1994a), regulation of splice site selection (Du et al. 1998; Xiao and Manley 1998; Prasad et al. 1999; Stojdl and Bell 1999; Pilch et al. 2001) and subcellular localization of splicing factors (Misteli and Spector 1996; Misteli et al. 1998). Several splicing factors are known to be phosphorylated in vivo, including a number of the serine/ arginine-rich (SR) protein family (Fu 1995; Graveley 2000), protein components of the small nuclear ribonucleoproteins (snRNPs; Tazi et al. 1993; Woppmann et al. 1993; Fetzer et al. 1997) and proteins associated with the spliceosome (SAPs; Gozani et al. 1994; Chiara et al. 1996; Reed 1996). Phosphorylation and dephosphorylation of these factors might act as a modulator of protein-protein (Xiao and Manley 1997) and protein-RNA interactions at multiple stages during the biogenesis of mRNAs (Tazi et al. 1997). A major advance towards understanding the regulation of pre-mRNA splicing by protein phosphorylation has been to isolate and characterize potential protein kinases and phosphatases that specifically target components of the splicing apparatus. We will review the molecular components of the splicing machinery which are affected by phosphorylation and consider the mechanisms by which specific kinases and phosphatases seem to contribute to a dynamic organization of pre-mRNA splicing factory, not only during transcription, but also in response to physiological stimuli.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Abovich N, Rosbash M (1997) Cross-intron bridging interactions in the yeast commitment complex are conserved in mammals. Cell 89: 403–412

    Article  PubMed  CAS  Google Scholar 

  • Akinaga S, Sugiyama K, Akiyama T (2000) UCN-01 (7-hydroxystaurosporine) and other indolocarbazole compounds: a new generation of anti-cancer agents for the new century? Anticancer Drug Des 15: 43–52

    PubMed  CAS  Google Scholar 

  • Akker SA, Smith PI, Chew SL (2001) Nuclear post-transcriptional control of gene expression. J Mol Endocrinol 27: 123–131

    Article  PubMed  CAS  Google Scholar 

  • Allemand E, Gattoni R, Bourbon HM, Stevenin J, Caceres JF, Soret J, Tazi J (2001) Distinctive features of Drosophila alternative splicing factor RS domain: implication for specific phosphorylation, shuttling, and splicing activation. Mol Cell Biol 21: 1345–1359

    Article  PubMed  CAS  Google Scholar 

  • Alsner J, Svejstrup JQ, Kjeldsen E, Sorensen BS, Westergaard 0 (1992) Identification of an N-terminal domain of eukaryotic DNA topoisomerase I dispensable for catalytic activity but essential for in vivo function. J Biol Chem 267: 12408–12411

    CAS  Google Scholar 

  • Amrein H, Gorman M, Nöthinger R (1988) The sex-determining gene tra-2 of Drosophila encodes a putative RNA binding domain. Cell 55: 1025–1035

    Article  PubMed  CAS  Google Scholar 

  • Amrein H, Hedley ML, Maniatis T (1994) The role of specific protein-RNA and protein-protein interactions in positive and negative control of pre-mRNA splicing by Transformer 2. Cell 76: 735–746

    Article  PubMed  CAS  Google Scholar 

  • Anizon F, Moreau P, Sancelme M, Voldoire A, Prudhomme M, Oilier M, Severe D, Riou JF, Bailly C, Fabbro D, Meyer T, Aubertin AM (1998) Syntheses, biochemical and biological evaluation of staurosporine analogues from the microbial metabolite rebeccamycin. Bioorg Med Chem 6: 1597–1604

    Article  PubMed  CAS  Google Scholar 

  • Arakawa H, Iguchi T, Morita M, Yoshinari T, Kojiri K, Suda H, Okura A, Nishimura S (1995) Novel indolocarbazole compound 6-N-formylamino-12,13-dihydro-1,11-dihydroxy-13-(beta-Dglucopyranosyl)-5H-indolo[2,3-a]pyrrolo-[3,4-c]carbazole-5,7(6H)-dione (NB-506): its potent antitumor activities in mice. Cancer Res 55: 1316–1320

    PubMed  CAS  Google Scholar 

  • Arning S, Gruter P, Bilbe G, Krämer A (1996) Mammalian splicing factor SF1 is encoded by variant cDNAs and binds to RNA. RNA 2: 794–810

    PubMed  CAS  Google Scholar 

  • Bailly C, Riou JF, Colson P, Houssier C, Rodrigues-Pereira E, Prudhomme M (1997) DNA cleavage by topoisomerase I in the presence of indolocarbazole derivatives of rebeccamycin. Biochemistry 36: 3917–3929

    Article  PubMed  CAS  Google Scholar 

  • Bailly C, Carrasco C, Hamy F, Vezin H, Prudhomme M, Saleem A, Rubin E (1999a) The camptothecin-resistant topoisomerase I mutant F361S is cross-resistant to antitumor rebeccamycin derivatives. A model for topoisomerase I inhibition by indolocarbazoles. Biochemistry 38: 8605–8611

    Google Scholar 

  • Bailly C, Dassonneville L, Colson P, Houssier C, Fukasawa K, Nishimura S, Yoshinari T (1999b) Intercalation into DNA is not required for inhibition of topoisomerase I by indolocarbazole antitumor agents. Cancer Res 59: 2853–2860

    PubMed  CAS  Google Scholar 

  • Barnard DC, Patton JG (2000) Identification and characterization of a novel serine-arginine-rich splicing regulatory protein. Mol Cell Biol 20: 3049–3057

    Article  PubMed  CAS  Google Scholar 

  • Barnett SF, Friedman DL, LeStourgeon WM (1989) The C protein of HeLa 40S nuclear ribonu- cleoprotein particles exist as anisotropic tetramers of (C1)3 C2. Mol Cell Biol 9: 492–498

    PubMed  CAS  Google Scholar 

  • Behrens SE, Galisson F, Legrain P, Luhrmann R (1993a) Evidence that the 60-kDa protein of 17S U2 small nuclear ribonucleoprotein is immunologically and functionally related to the yeast PRP9 splicing factor and is required for the efficient formation of prespliceosomes. Proc Natl Acad Sci USA 90: 8229–8233

    Article  PubMed  CAS  Google Scholar 

  • Behrens SE, Tyc K, Kastner B, Reichelt J, Lührmann R (1993b) Small nuclear ribonucleoprotein (RNP) U2 contains numerous additional proteins and has a bipartite RNP structure under splicing conditions. Mol Cell Biol 13: 307–319

    PubMed  CAS  Google Scholar 

  • Ben-David Y, Letwin K, Tannock L, Bernstein A, Pawson T (1991) A mammalian protein kinase with potential for serine/threonine and tyrosine phosphorylation is related to cell cycle regulators. EMBO J 10: 317–325

    PubMed  CAS  Google Scholar 

  • Bender J, Fink GR (1994) AFC1, a LAMMER kinase from Arabidopsis thaliana, activates STE12dependent processes in yeast. Proc Natl Acad Sci USA 91: 12105–12109

    Article  PubMed  CAS  Google Scholar 

  • Bennett M, Reed R (1993) Correspondence between a mammalian spliceosome component and an essential yeast splicing factor. Science 262: 105–108

    Article  PubMed  CAS  Google Scholar 

  • Bennett M, Michaud S, Kingston J, Reed R (1992) Protein components specifically associated with prespliceosome and spliceosome complexes. Genes Dev 6: 1986–2000

    Article  PubMed  CAS  Google Scholar 

  • Berget SM, Moore C, Sharp PA (1977) Spliced segments at the 5’ terminus of adenovirus 2 late mRNA. Proc Natl Acad Sci USA 74: 3171–3175

    Article  PubMed  CAS  Google Scholar 

  • Berglund JA, Chua K, Abovich N, Reed R, Rosbash M (1997) The splicing factor BBP interacts specifically with the pre-mRNA branchpoint sequence UACUAAC. Cell 89: 781–787

    Article  PubMed  CAS  Google Scholar 

  • Berglund JA, Abovich N, Rosbash M (1998) A cooperative interaction between U2AF65 and mBBP/SF1 facilitates branchpoint region recognition. Genes Dev 12: 858–867

    Article  PubMed  CAS  Google Scholar 

  • Beyer AL, Christensen ME, Walker BW, LeStourgeon WM (1977) Identification and characterization of the packaging proteins of core 40S hnRNP particles. Cell 11: 127–138

    Article  PubMed  CAS  Google Scholar 

  • Bharti AK, Olson MOJ, Kufe DW, Rubin EH (1996) Identification of a Nucleolin binding site in human topoisomerase I. J Biol Chem 271: 1993–1996

    Article  PubMed  CAS  Google Scholar 

  • Bindereif A, Green MR (1986) Ribonucleoprotein complex formation during pre-mRNA splicing in vitro. Mol Cell Biol 6: 2582–2592

    PubMed  CAS  Google Scholar 

  • Bindereif A, Green MR (1987) An ordered pathway of snRNP binding during mammalian premRNA splicing complex assembly. EMBO J 6: 2415–2424

    PubMed  CAS  Google Scholar 

  • Black DL, Pinto AL (1989) U5 small nuclear ribonucleoprotein: RNA structure analysis and ATP-dependent interaction with U4/U6. Mol Cell Biol 9: 3350–3359

    PubMed  CAS  Google Scholar 

  • Blencowe BJ, Issner R, Nickerson JA, Sharp PA (1998) A coactivator of pre-mRNA splicing. Genes Dev 12: 996–1009

    Article  PubMed  CAS  Google Scholar 

  • Boggs RT, Gregor P, Idriss S, Belote JM, McKeown M (1987) Regulation of sexual differentiation in D. melanogaster via alternative splicing of RNA from the transformer gene. Cell 50: 739–747

    Article  PubMed  CAS  Google Scholar 

  • Brill SJ, DiNardo S, Voelkel-Meiman K, Sternglanz R (1987) Need for DNA topoisomerase activity as a swivel for DNA replication and for transcription of ribosomal DNA. Nature 326: 414–416

    Article  PubMed  CAS  Google Scholar 

  • Brody E, Abelson J (1985) The “spliceosome”: yeast pre-messenger RNA associates with a 40S complex in a splicing-dependent reaction. Science 228: 963–967

    Article  PubMed  CAS  Google Scholar 

  • Brosi R, Hauri HP, Krämer A (1991) Separation of splicing factor SF3 into two components and purification of SF3a activity. J Biol Chem 268: 17640–17646

    Google Scholar 

  • Brosi R, Gröning K, Behrens SE, Lührmann R, Krämer A (1993) Interaction of mammalian splicing factor SF3a with U2 snRNP and relation of its 60-kD subunit to yeast PRP9. Science 262: 102–105

    Article  PubMed  CAS  Google Scholar 

  • Buckwalter CA, Lin AH, Tanizawa A, Pommier YG, Cheng YC, Kaufmann SH (1996) RNA synthesis inhibitors alter the subnuclear distribution of DNA topoisomerase I. Cancer Res 56: 1674–1681

    Google Scholar 

  • Burd CG, Dreyfuss G (1994) RNA binding specificity of hnRNP Al: significance of hnRNP Al high-affinity binding sites in pre-mRNA splicing. EMBO J 13: 1197–1204

    PubMed  CAS  Google Scholar 

  • Buvoli M, Cobianchi F, Biamonti G, Riva S (1990) Recombinant hnRNP protein Al and its N-terminal domain show preferential affinity for oligodeoxynucleotides homologous to intron/ exon acceptor sites. Nucleic Acids Res 18: 6595–6600

    Article  PubMed  CAS  Google Scholar 

  • Buvoli M, Cobianchi F, Riva S (1992) Interaction of hnRNP Al with snRNPs and pre-mRNAs: evidence for a possible role of Al RNA annealing activity in the first steps of spliceosome assembly. Nucleic Acids Res 20: 5017–5025

    Article  PubMed  CAS  Google Scholar 

  • Caceres JF, Krainer AR (1993) Functional analysis of pre-mRNA splicing factor SF2/ASF structural domains. EMBO J 12: 4715–4726

    PubMed  CAS  Google Scholar 

  • Caceres JF, Stamm S, Helfman DM, Krainer AR (1994) Regulation of alternative splicing in vivo by overexpression of antagonistic splicing factors. Science 265: 1706–1709

    Article  PubMed  CAS  Google Scholar 

  • Caceres JF, Misteli T, Screaton GR, Spector DL, Krainer AR (1997) Role of the modular domains of SR proteins in subnuclear localization and alternative splicing specificity. J Cell Biol 138: 225–238

    Article  PubMed  CAS  Google Scholar 

  • Cao W, Jamison SF, Garcia-Blanco MA (1997) Both phosphorylation and dephosphorylation of ASF/SF2 are required for pre-mRNA splicing in vitro. RNA 3: 1456–1467

    PubMed  CAS  Google Scholar 

  • Cardinali B, Cohen PTW, Lamond AI (1994) Protein phosphatase 1 can modulate alternative 5’ splice site selection in a HeLa splicing extract. FEBS Lett 352: 276–280

    Article  PubMed  CAS  Google Scholar 

  • Cavalli G, Bachmann D, Thoma F (1996) Inactivation of topoisomerases affects transcription-dependent chromatin transitions in rDNA but not in a gene transcribed by RNA polymerase II. EMBO J 15: 590–597

    PubMed  CAS  Google Scholar 

  • Chalfant CE, Mischak H, Watson JE, Winkler BC, Goodnight J, Farese RV, Cooper DR (1995) Regulation of alternative splicing of protein kinase C beta by insulin. J Biol Chem 270: 13326–13332

    Article  PubMed  CAS  Google Scholar 

  • Champoux JJ (1988) Topoisomerase I is preferentially associated with isolated replicating simian virus 40 molecules after treatment of infected cells with camptothecin. J Virol 62: 3675–3683

    PubMed  CAS  Google Scholar 

  • Champoux JJ (1992) Topoisomerase I is preferentially associated with normal SV40 replicative intermediates, but is associated with both replicating and nonreplicating SV40 DNAs which are deficient in histones. Nucleic Acids Res 20: 3347–3352

    Article  PubMed  CAS  Google Scholar 

  • Cheng SC, Abelson J (1987) Spliceosome assembly in yeast. Genes Dev 1: 1014–1027

    Article  PubMed  CAS  Google Scholar 

  • Chiara MD, Champion-Arnaud P, Buvoli M, Nadal-Ginard B, Reed R (1994) Specific protein protein interactions between the essential mammalian spliceosome-associated proteins SAP 61 and SAP 114. Proc Natl Acad Sci USA 91: 6403–6407

    Article  PubMed  CAS  Google Scholar 

  • Chiara MD, Gozani O, Bennett M, Champion-Arnaud P, Palandjian L, Reed R (1996) Identification of proteins that interact with exon sequences, splice sites, and the branchpoint sequence during each stage of spliceosome assembly. Mol Cell Biol 16: 3317–3326

    PubMed  CAS  Google Scholar 

  • Choi YD, Grabowski PJ, Sharp PA, Dreyfuss G (1986) Heterogeneous nuclear ribonucleoproteins: role in RNA splicing. Science 231: 1534–1539

    Article  PubMed  CAS  Google Scholar 

  • Cobianchi F, Calvio C, Stoppini M, Buvoli M, Riva S (1993) Phosphorylation of human hnRNP protein Al abrogates in vitro strand annealing activity. Nucleic Acids Res 21: 949–955

    Article  PubMed  CAS  Google Scholar 

  • Colwill K, Pawson T, Andrews B, Prasad J, Manley J, Bell JC, Duncan PI (1996a) The Clk/Sty protein kinase phosphorylates SR splicing factors and regulates their intranuclear distribution. EMBO J 15: 265–275

    PubMed  CAS  Google Scholar 

  • Colwill K, Feng LL, Yeakley JM, Gish GD, Caceres JF, Pawson T, Fu XD (1996b) SRPK1 and Clk/Sty protein kinases show distinct substrate specificities for serine/arginine-rich splicing factors. J Biol Chem 271: 24569–24575

    Article  PubMed  CAS  Google Scholar 

  • Cowper AE, Caceres JF, Mayeda A, Screaton GR (2001) Serine-arginine (SR) protein-like factors that antagonize authentic SR proteins and regulate alternative splicing. J Biol Chem 276: 48908–48914

    Google Scholar 

  • D’Arpa P, Machlin PS, Ratrie H, Rothfield NF, Cleveland DW, Earnshaw WC (1988) cDNA cloning of human DNA topoisomerase I: catalytic activity of a 67.7-kDa carboxyl-terminal fragment. Proc Natl Acad Sci USA 85: 2543–2547

    Google Scholar 

  • D’Arpa P, Liu LF (1989) Topoisomerase-targeting antitumor drugs. Biochim Biophys Acta 989: 163–177

    Google Scholar 

  • Du C, McGuffin ME, Dauwalder B, Rabinow L, Mattox W (1998) Protein phosphorylation plays an essential role in the regulation of alternative splicing and sex determination in Drosophila. Mol Cell 2: 741–750

    Article  PubMed  CAS  Google Scholar 

  • Duncan PI, Howell BW, Marius RM, Drmanic S, Douville EM, Bell JC (1995) Alternative splicing of STY, a nuclear dual specificity kinase. J Biol Chem 270: 21524–21531

    Article  PubMed  CAS  Google Scholar 

  • Duncan PI, Stojdl DF, Marius RM, Bell JC (1997) In vivo regulation of alternative pre-mRNA splicing by the Clkl protein kinase. Mol Cell Biol 17: 5996–6001

    PubMed  CAS  Google Scholar 

  • Eperon IC, Ireland DC, Smith RA, Mayeda A, Krainer AR (1993) Pathways for selection of 5’ splice sites by Ul snRNPs and SF2/ASF. EMBO J 12: 3607–3617

    PubMed  CAS  Google Scholar 

  • Eperon IC, Makarova OV, Mayeda A, Munroe SH, Caceres JF, Hayward DG, Krainer AR (2000) Selection of alternative 5’ splice sites: role of Ul snRNP and models for the antagonistic effects of SF2/ASF and hnRNP Al. Mol Cell Biol 20: 8303–8318

    Article  PubMed  CAS  Google Scholar 

  • Erez 0, Kahana C (2001) Screening for modulators of spermine tolerance identifies Skyl, the SR protein kinase of Saccharomyces cerevisiae, as a regulator of polyamine transport and ion homeostasis. Mol Cell Biol 21: 175–184

    Article  PubMed  CAS  Google Scholar 

  • Fetzer S, Lauber J, Will CL, Luhrmann R (1997) The [U4/U6.U5] tri-snRNP-specific 27K protein is a novel SR protein that can be phosphorylated by the snRNP-associated protein kinase. RNA 3: 344–355

    PubMed  CAS  Google Scholar 

  • Fleischmann G, Pflugfelder G, Steiner EK, Javaherian K, Howard GC, Wang JC, Elgin SCR (1984) Drosophila DNA topoisomerase I is associated with transcriptionally active regions of the genome. Proc Natl Acad Sci USA 81: 6958–6962

    Article  PubMed  CAS  Google Scholar 

  • Forné T, Rossi F, Labourier E, Antoine E, Cathala G, Brunel C, Tazi J (1995) Disruption of base-paired U4.U6 small nuclear RNAs induced by mammalian heterogeneous nuclear ribonucleoprotein C protein. J Biol Chem 270: 16476–16481

    Article  PubMed  Google Scholar 

  • Frendewey D, Keller W (1985) Stepwise assembly of a pre-mRNA splicing complex requires UsnRNPs and specific intron sequences. Cell 42: 355–367

    Article  PubMed  CAS  Google Scholar 

  • Fromont-Racine M, Rain JC, Legrain P (1997) Toward a functional analysis of the yeast genome through exhaustive two-hybrid screens. Nat Genet 16: 277–282

    Article  PubMed  CAS  Google Scholar 

  • Fu XD (1995) The superfamily of arginine/serine-rich splicing factors. RNA 1: 663–680

    PubMed  CAS  Google Scholar 

  • Fu XD, Maniatis T (1992) Isolation of a complementary DNA that encodes the mammalian splicing factor SC35. Science 256: 535–538

    Article  PubMed  CAS  Google Scholar 

  • Fukasawa K, Komatani H, Hara Y, Suda H, Okura A, Nishimura S, Yoshinari T (1998) Sequence-selective DNA cleavage by a topoisomerase I poison, NB-506. Int J Cancer 75: 145–150

    Article  PubMed  CAS  Google Scholar 

  • Fung PA, Labrecque R, Pederson T (1997) RNA-dependent phosphorylation of a nuclear RNA binding protein. Proc Natl Acad Sci USA 94: 1064–1068

    Article  PubMed  CAS  Google Scholar 

  • Gama-Carvalho M, Carvalho MP, Kehlenbach A, Valcarcel J, Carmo-Fonseca M (2001) Nucleocytoplasmic shuttling of heterodimeric splicing factor U2AE J Biol Chem 276: 13104–13112

    CAS  Google Scholar 

  • Garg LC, DiAngelo S, Jacob ST (1987) Role of DNA topoisomerase I in the transcription of super-coiled rRNA gene. Proc Natl Acad Sci USA 84: 3185–3188

    Article  PubMed  CAS  Google Scholar 

  • Ge H, Zuo P, Manley JL (1991) Primary structure of the human splicing factor ASF reveals similarities with Drosophila regulators. Cell 66: 373–382

    Article  PubMed  CAS  Google Scholar 

  • Georgatos SD, Stournaras C, Blobel G (1988) Heterotypic and homotypic associations between the nuclear lamins: site-specificity and control by phosphorylation. Proc Natl Acad Sci USA 85: 4325–4329

    Article  PubMed  CAS  Google Scholar 

  • Ghetti A, Pinol-Roma S, Michael WM, Morandi C, Dreyfuss G (1992) hnRNP I, the polypyrimidine tract-biding protein: distinct nuclear localization and association with hnRNAs. Nucleic Acids Res 20: 3671–3678

    Google Scholar 

  • Gilbert W, Siebel CW, Guthrie C (2001) Phosphorylation by Skylp promotes Npl3p shuttling and mRNA dissociation. RNA 7: 302–313

    Article  PubMed  CAS  Google Scholar 

  • Gilmour DS, Pflugfelder G, Wang JC, Lis JT (1986) Topoisomerase I interacts with transcribed regions in Drosophila cells. Cell 44: 401–407

    Article  PubMed  CAS  Google Scholar 

  • Goralski TJ, Edström JE, Baker BS (1989) The sex determination locus transformer-2 of Drosophila encodes a polypeptide with similarity to RNA binding protein. Cell 56: 1011–1018

    Article  PubMed  CAS  Google Scholar 

  • 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: 3356–3367

    PubMed  CAS  Google Scholar 

  • Gozani 0, Feld R, Reed R (1996) Evidence that sequence-independent binding of highly conserved U2 snRNP proteins upstream of the branch site is required for assembly of spliceosomal complex A. Genes Dev 10: 233–243

    Article  PubMed  CAS  Google Scholar 

  • Gozani O, Potashkin J, Reed R (1998) A potential role for U2AF-SAP 155 interactions in recruiting U2 snRNP to the branch site. Mol Cell Biol 18: 4752–4760

    PubMed  CAS  Google Scholar 

  • Grabowski PJ, Sharp PA (1986) Affinity chromatography of splicing complexes: U2, U5, and U4+U6 small nuclear ribonucleoprotein particles in the spliceosome. Science 233: 1294–1299

    Article  PubMed  CAS  Google Scholar 

  • Grabowski PJ, Padgett RA, Sharp PA (1984) Messenger RNA splicing in vitro: an excised intervening sequence and a potential intermediate. Cell 37: 415–427

    Article  PubMed  CAS  Google Scholar 

  • Grabowski PJ, Seiler SR, Sharp PA (1985) A multicomponent complex is involved in the splicing of messenger RNA precursors. Cell 42: 345–353

    Article  PubMed  CAS  Google Scholar 

  • Graveley BR (2000) Sorting out the complexity of SR protein functions. RNA 6: 1197–1211

    Article  PubMed  CAS  Google Scholar 

  • Graveley BR, Hertel KJ, Maniatis T (2001) The role of U2AF35 and U2AF65 in enhancer-dependent splicing. RNA 7: 806–818

    Article  PubMed  CAS  Google Scholar 

  • Gudi T, Lohmann SM, Pilz RB (1997) Regulation of gene expression by cyclic GMP-dependent protein kinase requires nuclear translocation of the kinase: identification of a nuclear localization signal. Mol Cell Biol 17: 5244–5254

    PubMed  CAS  Google Scholar 

  • Gui JF, Lane WS, Fu XD (1994a) A serine kinase regulates intracellular localization of splicing factors in the cell cycle. Nature 369: 678–682

    Article  PubMed  CAS  Google Scholar 

  • Gui J-F, Tronchère H, Chandler SD, Fu X-D (1994b) Purification and characterization of a kinase specific for the serine-and arginine-rich pre-mRNA splicing factors. Proc Natl Acad Sci USA 91: 10824–10828

    Article  PubMed  CAS  Google Scholar 

  • Gupta M, Fujimori A, Pommier Y (1995) Eukaryotic DNA topoisomerases I. Biochim Biophys Acta 1262: 1–14

    Article  PubMed  Google Scholar 

  • Guth S,Valcarcel J (2000) Kinetic role for mammalian SF1/BBP in spliceosome assembly and function after polypyrimidine tract recognition by U2AF. J Biol Chem 275: 38059–38066

    Article  Google Scholar 

  • Guthrie C, Patterson B (1988) Spliceosomal snRNAs. Annu Rev Genet 22: 387–419

    Article  PubMed  CAS  Google Scholar 

  • Hanes J, Von der Kammer H, Klaudiny J, Scheit KH (1994) Characterization by cDNA cloning of two new human protein kinases: evidence by sequence comparison of a new family of mammalian protein kinases. J Mol Biol 244: 665–672

    Article  PubMed  CAS  Google Scholar 

  • Hartmann AM, 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: 80–90

    Article  PubMed  CAS  Google Scholar 

  • Heinrichs V, Bach M, Winkelmann G, Lührmann R (1990) U1-specific protein C needed for efficient complex formation of Ul snRNP with a 5’ splice site. Science 247: 69–72

    Article  PubMed  CAS  Google Scholar 

  • Heinrichs V, Ryner LC, Baker BS (1998) Regulation of sex-specific selection of fruitless 5’ splice sites by transformer and transformer-2. Mol Cell Biol 18: 450–458

    PubMed  CAS  Google Scholar 

  • Hogges PE, Beggs JD (1994) U2 fulfills a commitment. Curr Biol 4: 264–267

    Article  Google Scholar 

  • Howell BW, Afar DE, Lew J, Douville EM, Icely PL, Gray DA, Bell JC (1991) STY, a tyrosinephosphorylating enzyme with sequence homology to serine/threonine kinases. Mol Cell Biol 11: 568–572

    PubMed  CAS  Google Scholar 

  • Huang Y, Steitz JA (2001) Splicing factors SRp20 and 9G8 promote the nucleocytoplasmic export of mRNA. Mol Cell 7: 899–905

    Article  PubMed  CAS  Google Scholar 

  • Idriss H, Kumar A, Casas-Finet JR, Guo H, Damuni Z, Wilson SH (1994) Regulation of in vitro nucleic acid strand annealing activity of heterogeneous nuclear ribonucleoprotein protein Al by reversible phosphorylation. Biochemistry 33: 11382–11390

    Article  PubMed  CAS  Google Scholar 

  • Jamison SF, Crow A, Garcia-Blanco MA (1992) The spliceosome assembly pathway in mammalian extracts. Mol Cell Biol 12: 4279–4287

    PubMed  CAS  Google Scholar 

  • Jamison SF, Pasman Z, Wang J, Will C, Lührmann R, Manley JL, Garcia-Blanco MA (1995) Ul snRNP-ASF/SF2 interaction and 5’ splice site recognition: characterization of required elements. Nucleic Acids Res 23: 3260–3267

    Article  PubMed  CAS  Google Scholar 

  • Jensen AD, Svejstrup JQ (1996) Purification and characterization of human topoisomerase I mutants. Eur J Biochem 236: 389–394

    Article  PubMed  CAS  Google Scholar 

  • Johnson KW, Smith KA (1991) Molecular cloning of a novel human cdc2/CDC28-like protein kinase. J Biol Chem 266: 3402–3407

    PubMed  CAS  Google Scholar 

  • Kanaar R, Roche SE, Beall EL, Green MR, Rio DC (1993) The conserved pre-mRNA splicing factor U2AF from Drosophila: requirement for viability. Science 262: 569–573

    Article  PubMed  CAS  Google Scholar 

  • Kandels-Lewis S, Séraphin B (1993) Role of U6 snRNA in 5’ splice site selection. Science 262: 2035–2039

    Article  PubMed  CAS  Google Scholar 

  • Kam J,Vidali G, Boffa LC, Allfrey VG (1977) Characterization of the non-histone nuclear proteins associated with rapidly labeled heterogeneous nuclear RNA. J Biol Chem 252: 7307–7322

    Google Scholar 

  • Kataoka N, Bachorik JL, Dreyfuss G (1999) Transportin-SR, a nuclear import receptor for SR proteins. J Cell Biol 145: 1145–1152

    Article  PubMed  CAS  Google Scholar 

  • Kohtz JD, Jamison SF, Will CL, Zuo P, Lührmann R, Garcia-Blanco MA, Manley JL (1994) Proteinprotein interactions and 5’-splice-site recognition in mammalian mRNA precursors. Nature 368: 119–124

    Article  PubMed  CAS  Google Scholar 

  • Koizumi J, Okamoto Y, Onogi H, Mayeda A, Krainer AR, Hagiwara M (1999) The subcellular localization of SF2/ASF is regulated by direct interaction with SR protein kinases ( SRPKs ). J Biol Chem 274: 11125–11131

    Google Scholar 

  • Kojima T, Zama T, Wada K, Onogi H, Hagiwara M (2001) Cloning of human PRP4 reveals interaction with Clkl. J Biol Chem 276: 32247–32256

    Article  PubMed  CAS  Google Scholar 

  • Konarska MM, Sharp PA (1986) Electrophoretic separation of complexes involved in the splicing of precursors to mRNAs. Cell 46: 845–855

    Article  PubMed  CAS  Google Scholar 

  • Konarska MM, Sharp PA (1987) Interactions between small nuclear ribonucleoprotein particles in formation of spliceosomes. Cell 49: 763–774

    Article  PubMed  CAS  Google Scholar 

  • Konforti BB, Koziolkiewicz MJ, Konarska MM (1993) Disruption of base pairing between the 5’ splice site and the 5’ end of Ul snRNA is required for spliceosome assembly. Cell 75: 863–873

    Article  PubMed  CAS  Google Scholar 

  • Konig H, Ponta H, Herrlich P (1998) Coupling of signal transduction to alternative pre-mRNA splicing by a composite splice regulator. EMBO J 17: 2904–2913

    Article  PubMed  CAS  Google Scholar 

  • Krainer AR, Maniatis T, Ruskin B, Green MR (1984) Normal and mutant human b-globin premRNAs are faithfully and efficiently spliced in vitro. Cell 36: 993–1005

    Article  PubMed  CAS  Google Scholar 

  • Krainer AR, Mayeda A, Kozak D, Binns G (1991) Functional expression of cloned human splicing factor SF2: homology to RNA-binding proteins, Ul 70K, and Drosophila splicing regulators. Cell 66: 383–394

    Article  PubMed  CAS  Google Scholar 

  • Krämer A (1996) The structure and function of proteins involved in mammalian pre-mRNA splicing. Annu Rev Biochem 65: 367–409

    Article  PubMed  Google Scholar 

  • Krämer A, Utans U (1991) Three protein factors (SF1, SF3 and U2AF) function in pre-splicing complex formation in addition to snRNPs. EMBO J 10: 1503–1509

    PubMed  Google Scholar 

  • Krämer A, Mulhauser F, Wersig C, Groning K, Bilbe G (1995) Mammalian splicing factor SF3a120 represents a new member of the SURP family of proteins and is homologous to the essential splicing factor PRP21p of Saccharomyces cerevisiae. RNA 1: 260–272

    PubMed  Google Scholar 

  • Krämer A, Gruter P, Groning K, Kastner B (1999) Combined biochemical and electron micro- scopic analyses reveal the architecture of the mammalian U2 snRNP. J Cell Biol 145: 1355–1368

    Article  PubMed  Google Scholar 

  • Kraus ME, Lis JT (1994) The concentration of B52, an essential splicing factor and regulator of splice site choice in vitro, is critical for Drosophila development. Mol Cell Biol 14: 5360–5370

    PubMed  CAS  Google Scholar 

  • Kretzschmar M, Meisterernst M, Roeder RG (1993) Identification of human DNA topoisomerase I as a cofactor for activator-dependent transcription by RNA polymerase II. Proc Natl Acad Sci USA 90: 11508–11512

    Article  PubMed  CAS  Google Scholar 

  • Kroeger PE, Rowe TC (1989) Interaction of topoisomerase I with the transcribed region of the Drosophila HSP 70 heat shock gene. Nucleic Acids Res 17: 8495–8509

    Article  PubMed  CAS  Google Scholar 

  • Kuhn AN, Li Z, Brow DA (1999) Splicing factor Prp8 governs U4/U6 RNA unwinding during activation of the spliceosome. Mol Cell 3: 65–75

    Article  PubMed  CAS  Google Scholar 

  • Kumar A, Wilson SH (1990) Studies of the strand-annealing activity of mammalian hnRNP complex protein Al. Biochemistry 29: 10717–10722

    Article  PubMed  CAS  Google Scholar 

  • Kumar A, Williams KR, Szer W (1986) Purification and domain structure of core hnRNP proteins Al and A2 and their relationship to single-stranded DNA-binding proteins. J Biol Chem 261: 11266–11273

    PubMed  CAS  Google Scholar 

  • Kuroyanagi N, Onogi H, Wakabayashi T, Hagiwara M (1998) Novel SR-protein-specific kinase, SRPK2, disassembles nuclear speckles. Biochem Biophys Res Commun 242: 357–364

    Article  PubMed  CAS  Google Scholar 

  • Kuroyanagi H, Kimura T, Wada K, Hisamoto N, Matsumoto K, Hagiwara M (2000) SPK-1, a C. elegans SR protein kinase homologue, is essential for embryogenesis and required for germline development. Mech Dev 99: 51–64

    Article  PubMed  CAS  Google Scholar 

  • Labourier E, Rossi F, Gallouzi IE, Allemand E, Divita G, Tazi J (1998) Interaction between the N-terminal domain of human DNA topoisomerase I and the arginine-serine domain of its substrate determines phosphorylation of SF2/ASF splicing factor. Nucleic Acids Res 26: 2955–2962

    Article  PubMed  CAS  Google Scholar 

  • Labourier E, Riou JF, Prudhomme M, Carrasco C, Bailly C, Tazi J (1999a) Poisoning of topoisomerase I by an antitumor indolocarbazole drug: stabilization of topoisomerase I-DNA covalent complexes and specific inhibition of the protein kinase activity. Cancer Res 59: 52–55

    PubMed  CAS  Google Scholar 

  • Labourier E, Bourbon HM, Gallouzi I, Fostier M, Allemand E, Tazi J (1999b) Antagonism between RSF1 and SR proteins for both splice site recognition in vitro and Drosophila development. Genes Dev 13: 740–753

    Article  PubMed  CAS  Google Scholar 

  • Labourier E, Allemand E, Brand S, Fostier M, Tazi J, Bourbon HM (1999c) Recognition of exonic splicing enhancer sequences by the Drosophila splicing repressor RSF1. Nucleic Acids Res 27: 2377–2386

    Article  PubMed  CAS  Google Scholar 

  • Lai MC, Lin RI, Huang SY, Tsai CW, Tarn WY (2000) A human importin-beta family protein, transportin-SR2, interacts with the phosphorylated RS domain of SR proteins. J Biol Chem 275: 7950–7957

    Article  PubMed  CAS  Google Scholar 

  • Lai MC, Lin RI, Tarn WY (2001) Transportin-SR2 mediates nuclear import of phosphorylated SR proteins. Proc Natl Acad Sci USA 98: 10154–10159

    Article  PubMed  CAS  Google Scholar 

  • Lamond AI, Konarska MM, Grabowski PJ, Sharp PA (1988) Spliceosome assembly involves the binding and release of U4 small nuclear ribonucleoprotein. Proc Natl Acad Sci USA 85: 411–415

    Article  PubMed  CAS  Google Scholar 

  • Lee K, Du C, Horn M, Rabinow L (1996) Activity and autophosphorylation of LAMMER protein kinases. J Biol Chem 271: 27299–27303

    Article  PubMed  CAS  Google Scholar 

  • Lee MP, Brawn SD, Chen A, Hsieh TS (1993) DNA topoisomerase I is essential in Drosophila melanogaster. Proc Natl Acad Sci USA 90: 6656–6660

    Article  PubMed  CAS  Google Scholar 

  • Legrain P, Chapon C (1993) Interaction between PRP11 and SPP91 yeast splicing factors and characterization of a PRP9–PRP11–SPP91 complex. Science 262: 108–110

    Article  PubMed  CAS  Google Scholar 

  • Legrain P, Séraphin B, Rosbash M (1988) Early commitment of yeast pre-mRNA to the spliceosome pathway. Mol Cell Biol 8: 3755–3760

    PubMed  CAS  Google Scholar 

  • Legrain P, Chapon C, Galisson F (1993) Interactions between PRP9 and SPP91 splicing factors identify a protein complex required in prespliceosome assembly. Genes Dev 7: 1390–1399

    Article  PubMed  CAS  Google Scholar 

  • Lerner MR, Boyle JA, Mount SM, Wolin SL, Steitz JA (1980) Are snRNPs involved in splicing? Nature 283: 220–224

    Article  PubMed  CAS  Google Scholar 

  • Lesser CF, Guthrie C (1993) Mutations in U6 snRNA that alter splice site specificity: implications for the active site. Science 262: 1982–1988

    Article  PubMed  CAS  Google Scholar 

  • Liu LF, Miller KG (1981) Eucaryotic DNA topoisomerases: two forms of type I DNA topoisomerases from HeLa cell nuclei. Proc Natl Acad Sci USA 78: 3487–3491

    Article  PubMed  CAS  Google Scholar 

  • Liu LF, Wang JC (1987) Supercoiling of the DNA template during transcription. Proc Natl Acad Sci USA 84: 7024–7027

    Article  PubMed  CAS  Google Scholar 

  • Lührmann R (1988) snRNP proteins. In: Birnstiel ML (ed) Structure and function of major and minor small nuclear ribonucleoprotein particles. Springer, Berlin Heidelberg New York, pp 71–99

    Book  Google Scholar 

  • Lührmann R, Kastner B, Bach M (1990) Structure of spliceosomal snRNPs and their role in premRNA splicing. Biochem Biophys Acta 1087: 265–292

    Article  PubMed  Google Scholar 

  • MacMillan AM, Query CC, Allerson CR, Chen S, Verdine GL, Sharp PA (1994) Dynamic association of proteins with the pre-mRNA branch region. Genes Dev 8: 3008–3020

    Article  PubMed  CAS  Google Scholar 

  • Madden KR, Champoux JJ (1992) Overexpression of human topoisomerase I in baby hamster kidney cells: hypersensitivity of clonal isolates to camptothecin. Cancer Res 52: 525–532

    PubMed  CAS  Google Scholar 

  • Madden KR, Stewart L, Champoux JJ (1995) Preferential binding of human topoisomerase Ito superhelical DNA. EMBO J 14: 5399–5409

    PubMed  CAS  Google Scholar 

  • Makarova OV, Makarov EM, Luhrmann R (2001) The 65 and 110 kDa SR-related proteins of the U4/U6.U5 tri-snRNP are essential for the assembly of mature spliceosomes. EMBO J 20: 2553–2563

    Article  PubMed  CAS  Google Scholar 

  • Mayeda A, Krainer AR (1992) Regulation of alternative pre-mRNA splicing by hnRNP Al and splicing factor SF2. Cell 68: 365–375

    Article  PubMed  CAS  Google Scholar 

  • Mayeda A, Helfman DM, Krainer AR (1993) Modulation of exon skipping and inclusion by heterogeneous nuclear ribonucleoprotein Aland pre-mRNA splicing factor SF2/ASE Mol Cell Biol 13: 2993–3001

    CAS  Google Scholar 

  • Mayeda A, Munroe SH, Càceres JF, Krainer AR (1994) Function of conserved domains of hnRNP Al and other hnRNP A/B proteins. EMBO J 13: 5483–5495

    PubMed  CAS  Google Scholar 

  • Mayrand SH, Pedersen N, Pederson T (1986) Identification of proteins that bind tightly to premRNA during in vitro splicing. Proc Natl Acad Sci USA 83: 3718–3722

    Article  PubMed  CAS  Google Scholar 

  • Mayrand SH, Dwen P, Pederson T (1993) Serine/threonine phosphorylation regulates binding of C hnRNP proteins to pre-mRNA. Proc Natl Acad Sci USA 90: 7764–7768

    Article  PubMed  CAS  Google Scholar 

  • Mayrand SH, Fung PA, Pederson T (1996) A discrete 3’ region of U6 small nuclear RNA modulates the phosphorylation cycle of the heterogeneous nuclear ribonucleoprotein particle protein. Mol Cell Biol 16: 1241–1246

    PubMed  CAS  Google Scholar 

  • Meier UT, Blobel G (1992) Nopp140 shuttles on tracks between nucleolus and cytoplasm. Cell 70: 127–138

    Article  PubMed  CAS  Google Scholar 

  • Menegay H, Moeslein F, Landreth G (1999) The dual specificity protein kinase CLK3 is abundantly expressed in mature mouse spermatozoa. Exp Cell Res 253: 463–473

    Article  PubMed  CAS  Google Scholar 

  • Merendino L, Guth S, Bilbao D, Martinez C, Valcarcel J (1999) Inhibition of msl-2 splicing by Sex-lethal reveals interaction between U2AF35 and the 3’ splice site AG. Nature 402: 838–841

    Article  PubMed  CAS  Google Scholar 

  • Merino A, Madden KR, Lane WS, Champoux JJ, Reinberg D (1993) DNA topoisomerase I is involved in both repression and activation of transcription. Nature 365: 227–232

    Article  PubMed  CAS  Google Scholar 

  • Mermoud JE, Cohen PTW, Lamond AI (1992) Ser/Thr-specific protein phosphatases are required for both catalytic steps of pre-mRNA splicing. Nucleic Acids Res 20: 5263–5269

    Article  PubMed  CAS  Google Scholar 

  • Mermoud JE, Calvio C, Lamond AI (1994a) Uncovering the role of Ser/Thr protein phosphorylation in nuclear pre-mRNA splicing. Adv Prot Phosphatases 8: 99–118

    CAS  Google Scholar 

  • Mermoud JE, Cohen PT, Lamond AI (1994b) Regulation of mammalian spliceosome assembly by a protein phosphorylation mechanism. EMBO J 13: 5679–5688

    PubMed  CAS  Google Scholar 

  • Michaud S, Reed R (1991) An ATP-independent complex commits pre-mRNA to the mammalian spliceosome assembly pathway. Genes Dev 5: 2534–2546

    Article  PubMed  CAS  Google Scholar 

  • Michaud S, Reed R (1993) A functional association between the 5’ and 3’ splice sites is established in the earliest prespliceosome complex ( E) in mammals. Genes Dev 7: 1008–1020

    Google Scholar 

  • Misteli T, Spector DL (1996) Serine/threonine phosphatase 1 modulates the subnuclear distribution of pre-mRNA splicing factors. Mol Biol Cell 7: 1559–1572

    PubMed  CAS  Google Scholar 

  • Misteli T, Caceres JF, Clement JQ, Krainer AR, Wilkinson MF, Spector DL (1998) Serine phosphorylation of SR proteins is required for their recruitment to sites of transcription in vivo. J Cell Biol 143: 297–307

    Article  PubMed  CAS  Google Scholar 

  • Morham SG, Kluckman KD, Voulomanos N, Smithies 0 (1996) Targeted disruption of the mouse topoisomerase I gene by camptothecin selection. Mol Cell Biol 16: 6804–6809

    CAS  Google Scholar 

  • Mount SM, Salz HK (2000) Pre-messenger RNA processing factors in the Drosophila genome. J Cell Biol 150: 37–44

    Article  Google Scholar 

  • Muller MT, Pfund WP, Mehta VB, Trask DK (1985) Eukaryotic type I topoisomerase is enriched in the nucleolus and catalytically active on ribosomal DNA. EMBO J 4: 1237–1243

    PubMed  CAS  Google Scholar 

  • Munroe SH, Dong XF (1992) Heterogeneous nuclear ribonucleoprotein Al catalyzes RNA: RNA annealing. Proc Natl Acad Sci USA 89: 895–899

    Google Scholar 

  • Murray HL, Jarrell KA (1999) Flipping the switch to an active spliceosome. Cell 96: 599–602

    Article  PubMed  CAS  Google Scholar 

  • Nabeshima K, Kurooka H, Takeuchi M, Kinoshita K, Nakaseko Y, Yanagida M (1995) p93disl, which is required for sister chromatid separation, is a novel microtubule and spindle pole body-associating protein phosphorylated at the Cdc2 target sites. Genes Dev 9: 1572 1585

    Google Scholar 

  • Nagai K (1996) RNA-protein complexes. Curr Opin Struct Biol 6: 53–61

    Article  PubMed  CAS  Google Scholar 

  • Nakielny S, Dreyfuss G (1996) The hnRNP C proteins contain a nuclear retention sequence that can override nuclear export signals. J Cell Biol 134: 1365–1373

    Article  PubMed  CAS  Google Scholar 

  • Nayler O, Stamm S, Ullrich A (1997) Characterization and comparison of four serine-and arginine-rich ( SR) protein kinases. Biochem J 326: 693–700

    Google Scholar 

  • Nayler O, Schnorrer F, Stamm S, Ullrich A (1998) The cellular localization of the murine serine/arginine-rich protein kinase CLK2 is regulated by serine 141 autophosphorylation. J Biol Chem 273: 34341–34348

    Article  PubMed  CAS  Google Scholar 

  • Nelson KK, Green MR (1989) Mammalian U2 snRNP has a sequence-specific RNA-binding activity. Genes Dev 3: 1562–1571

    Article  PubMed  CAS  Google Scholar 

  • Nikolakaki E, Kohen R, Hartmann AM, Stamm S, Georgatsou E, Giannakouros T (2001) Cloning and characterization of an alternatively spliced form of SR protein kinase 1 that interacts specifically with scaffold attachment factor-B. J Biol Chem 276: 40175–40182

    PubMed  CAS  Google Scholar 

  • Nolen B, Yun CY, Wong CF, McCammon JA, Fu XD, Ghosh G (2001) The structure of Skylp reveals a novel mechanism for constitutive activity. Nat Struct Biol 8: 176–183

    Article  PubMed  CAS  Google Scholar 

  • Ohkubo M, Nishimura T, Kawamoto H, Nakano M, Honma T, Yoshinari T, Arakawa H, Suda H, Morishima H, Nishimura S (2000) Synthesis and biological activities of NB-506 analogues modified at the glucose group. Bioorg Med Chem Lett 10: 419–422

    Article  PubMed  CAS  Google Scholar 

  • Ono Y, Kikkawa U, Ogita K, Fujii T, Kurokawa T, Asaoka Y, Sekiguchi K,Ase K, Igarashi K, Nishizuka Y (1987) Expression and properties of two types of protein kinase C: alternative splicing from a single gene. Science 236: 1116–1120

    CAS  Google Scholar 

  • Padgett RA, Konarska MM, Grabowski PJ, Hardy SF, Sharp PA (1984) Lariat RNAs as intermediates and products in the splicing of messenger RNA precursors. Science 225: 898–903

    Article  PubMed  CAS  Google Scholar 

  • Padmanabha R, Gehrung S, Snyder M (1991) The KNS1 gene of Saccharomyces cerevisiae encodes a nonessential protein kinase homologue that is distantly related to members of the CDC28/cdc2 gene family. Mol Gen Genet 229: 1–9

    Article  PubMed  CAS  Google Scholar 

  • Papoutsopoulou S, Nikolakaki E, Chalepakis G, Kruft V, Chevaillier P, Giannakouros T (1999) SR protein-specific kinase 1 is highly expressed in testis and phosphorylates protamine 1. Nucleic Acids Res 27: 2972–2980

    Article  PubMed  CAS  Google Scholar 

  • Patel NA, Chalfant CE, Watson JE, Wyatt JR, Dean NM, Eichler DC, Cooper DR (2001) Insulin regulates alternative splicing of protein kinase C beta II through a phosphatidylinositol 3-kinasedependent pathway involving the nuclear serine/arginine-rich splicing factor, SRp40, in skeletal muscle cells. J Biol Chem 276: 22648–22654

    Article  PubMed  CAS  Google Scholar 

  • Patton JG, Mayer SA, Tempst P, Nadal-Ginard B (1991) Characterization and molecular cloning of polypyrimidine tract-binding protein: a component of a complex necessary for pre-mRNA splicing. Genes Dev 5: 1237–1251

    Article  PubMed  CAS  Google Scholar 

  • 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: 393–406

    Article  PubMed  CAS  Google Scholar 

  • Pederson T (1974) Proteins associated with heterogeneous nuclear RNA in eukaryotic cells. J Mol Biol 83: 163–183

    Article  PubMed  CAS  Google Scholar 

  • Peled-Zehavi H, Berglund JA, Rosbash M, Frankel AD (2001) Recognition of RNA branch point sequences by the KH domain of splicing factor 1 (mammalian branch point binding protein) in a splicing factor complex. Mol Cell Biol 21: 5232–5241

    Article  PubMed  CAS  Google Scholar 

  • Petersen-Mahrt SK, Estmer C, Ohrmalm C, Matthews DA, Russell WC, Akusjarvi G (1999) The splicing factor-associated protein, p32, regulates RNA splicing by inhibiting ASF/SF2 RNA binding and phosphorylation. EMBO J 18: 1014–1024

    Article  PubMed  CAS  Google Scholar 

  • Pikielny CW, Rosbash M (1986) Specific small nuclear RNAs are associated with yeast spliceosomes. Cell 45: 869–877

    Article  PubMed  CAS  Google Scholar 

  • Pilch B, Allemand E, Facompre M, Bailly C, Riou JF, Soret J, Tazi J (2001) Specific inhibition of serine-and arginine-rich splicing factors phosphorylation, spliceosome assembly, and splicing by the antitumor drug NB-506. Cancer Res 61: 6876–6884

    PubMed  CAS  Google Scholar 

  • Pinol-Roma S, Dreyfuss G (1991) Transcription-dependent and transcription-independent nuclear transport of hnRNP proteins. Science 253: 312–317

    Article  PubMed  CAS  Google Scholar 

  • Pinol-Roma S, Dreyfuss G (1992) Shuttling of pre-mRNA binding proteins between nucleus and cytoplasm. Nature 355: 730–732

    Article  PubMed  CAS  Google Scholar 

  • Pommier Y (1996) Eukaryotic DNA topoisomerase I: genome gatekeeper and its intruders, camptothecins. Semin Oncol 23: 3–10

    PubMed  CAS  Google Scholar 

  • Pommier Y, Pourquier P, Fan Y, Strumberg D (1998) Mechanism of action of eukaryotic DNA topoisomerase I and drugs targeted to the enzyme. Biochim Biophys Acta 1400: 83105

    Google Scholar 

  • Pontius BW, Berg P (1990) Renaturation of complementary DNA strands mediated by purified mammalian heterogeneous nuclear ribonucleoprotein Al protein: implications for a mechanism for rapid molecular assembly. Proc Natl Acad Sci USA 87: 8403–8407

    Article  PubMed  CAS  Google Scholar 

  • Pontius BW, Berg P (1992) Rapid assembly and disassembly of complementary DNA strands through an equilibrium intermediate state mediated by Al hnRNP protein. J Biol Chem 267: 13815–13818

    PubMed  CAS  Google Scholar 

  • Pourquier P, Takebayashi Y, Urasaki Y, Gioffre C, Kohlhagen G, Pommier Y (2000) Induction of topoisomerase I cleavage complexes by 1-beta-D-arabinofuranosylcytosine (ara-C) in vitro and in ara-C-treated cells. Proc Natl Acad Sci USA 97: 1885–1890

    Article  PubMed  CAS  Google Scholar 

  • Prasad J, Colwill K, Pawson T, Manley JL (1999) The protein kinase Clk/Sty directly modulates SR protein activity: both hyper-and hypophosphorylation inhibit splicing. Mol Cell Biol 19: 6991–7000

    PubMed  CAS  Google Scholar 

  • Query CC, Bentley RC, Keene JD (1989) A common RNA recognition motif identified within a defined Ul RNA binding domain of the 70K U1 snRNP protein. Cell 57: 89–101

    Article  PubMed  CAS  Google Scholar 

  • Query CC, Strobel SA, Sharp PA (1996) Three recognition events at the branch-site adenine. EMBO J 15: 1392–1402

    PubMed  CAS  Google Scholar 

  • Rabinow L, Birchler JA (1989) A dosage-sensitive mod ifier of retrotransposon-induced alleles of the Drosophila white locus. EMBO J 8: 879–889

    PubMed  CAS  Google Scholar 

  • Rabinow L, Chiang SL, Birchler JA (1993) Mutations at the Darkener of apricot locus modulate transcript levels of copia and copia-induced mutations in Drosophila melanogaster. Genetics 134: 1175–1185

    PubMed  CAS  Google Scholar 

  • Rain JC, Tartakoff AM, Krämer A, Legrain P (1996) Essential domains of the PRP21 splicing factor are implicated in the binding to PRP9 and PRP11 proteins and are conserved through evolution. RNA 2: 535–550

    PubMed  CAS  Google Scholar 

  • Rain JC, Rafi Z, Rhani Z, Legrain P, Krämer A (1998) Conservation of functional domains involved in RNA binding and protein-protein interactions in human and Saccharomyces cerevisiae premRNA splicing factor SF1. RNA 4: 551–565

    Article  PubMed  CAS  Google Scholar 

  • Reed R (1996) Initial splice-site recognition and pairing during pre-mRNA splicing. Curr Opin Genet Dev 6: 215–220

    Article  PubMed  CAS  Google Scholar 

  • Reed R, Griffith J, Maniatis T (1988) Purification and visualization of native spliceosomes. Cell 53: 949–961

    Article  PubMed  CAS  Google Scholar 

  • Ring HZ, Lis JT (1994) The SR protein B52/SRp55 is essential for Drosophila development. Annu Rev Cell Biol 9: 265–315

    Google Scholar 

  • Rogers J, Wall R (1980) A mechanism for RNA splicing. Proc Natl Acad Sci USA 77: 1877–1879

    Article  PubMed  CAS  Google Scholar 

  • Roscigno RF, Garcia-Blanco MA (1995) SR proteins escort the U4/U6.U5 tri-snRNP to the spliceosome. RNA 1: 692–706

    PubMed  CAS  Google Scholar 

  • Rose KM, Szopa J, Han FS, Cheng YC, Richter A, Scheer U (1988) Association of DNA topoisomerase I and RNA polymerase I: a possible role for topoisomerase I in ribosomal gene transcription. Chromosoma 96: 411–416

    Article  PubMed  CAS  Google Scholar 

  • Rossi F, Labourier E, Forné T, Divita G, Derancourt J, Riou JF, Antoine E, Cathala G, Brunel C, Tazi J (1996a) Specific phosphorylation of SR proteins by mammalian DNA topoisomerase I. Nature 381: 80–82

    Article  PubMed  CAS  Google Scholar 

  • Rossi F, Forné T, Antoine E, Tazi J, Brunel C, Cathala G (1996b) Involvement of Ul small nuclear ribonucleoproteins (snRNP) in 5’ splice site-U1 snRNP interaction. J Biol Chem 271: 23985–23991

    Google Scholar 

  • Rossi F, Labourier E, Gallouzi IE, Derancourt J, Allemand E, Divita G, Tazi J (1998) The C-terminal domain but not the tyrosine 723 of human DNA topoisomerase I active site contributes to kinase activity. Nucleic Acids Res 26: 2963–2970

    Article  PubMed  CAS  Google Scholar 

  • Roth MB, Gall JG (1987) Monoclonal antibodies that recognize transcription unit proteins on newt lampbrush chromosomes. J Cell Biol 105: 1047–1054

    Article  PubMed  CAS  Google Scholar 

  • Roth MB, Murphy C, Gall JG (1990) A monoclonal antibody that recognizes a phosphorylated epitope stains lampbrush chromosome loops and small granules in the amphibian germinal vesicle. J Cell Biol 111: 2217–2223

    Article  PubMed  CAS  Google Scholar 

  • Roth MB, Zahler AM, Stolk JA (1991) A conserved family of nuclear phosphoproteins localized to sites of polymerase II transcription. J Cell Biol 115: 587–591

    Article  PubMed  CAS  Google Scholar 

  • Ruby SW, Abelson J (1988) An early hierarchic role of Ul small nuclear ribonucleoprotein in spliceosome assembly. Science 242: 1028–1035

    Article  PubMed  CAS  Google Scholar 

  • Rudner DZ, Kanaar R, Breger KS, Rio DC (1996) Mutations in the small subunit of the Drosophila U2AF splicing factor cause lethality and developmental defects. Proc Natl Acad Sci USA 93: 10333–10337

    Article  PubMed  CAS  Google Scholar 

  • Rudner DZ, Breger KS, Rio DC (1998a) Molecular genetic analysis of the heterodimeric splicing factor U2AF: the RS domain on either the large or small Drosophila subunit is dispensable in vivo. Genes Dev 12: 1010–1021

    Article  PubMed  CAS  Google Scholar 

  • Rudner DZ, Kanaar R, Breger KS, Rio DC (1998b) Interaction between subunits of heterodimeric splicing factor U2AF is essential in vivo. Mol Cell Biol 18: 1765–1773

    PubMed  CAS  Google Scholar 

  • Ruskin B, Krainer AR, Maniatis T, Green MR (1984) Excision of an intact intron as a novel lariat structure during pre-mRNA splicing in vitro. Cell 38: 317–331

    Article  PubMed  CAS  Google Scholar 

  • Ruskin B, Zamore PD, Green MR (1988) A factor, U2AF, is required for U2 snRNP binding and splicing complex assembly. Cell 52: 207–219

    Article  PubMed  CAS  Google Scholar 

  • Ryner LC, Goodwin SF, Castrillon DH, Anand A, Villella A, Baker BS, Hall JC, Taylor BJ, Wasserman SA (1996) Control of male sexual behavior and sexual orientation in Drosophila by the fruitless gene. Cell 87: 1079–1089

    Article  PubMed  CAS  Google Scholar 

  • Sanford JR, Bruzik JP (1999) Developmental regulation of SR protein phosphorylation and activity. Genes Dev 13: 1513–1518

    Article  PubMed  CAS  Google Scholar 

  • Sawa H, Abelson J (1992) Evidence for a base-pairing interaction between U6 small nuclear RNA and the 5’ splice site during the splicing reaction in yeast. Proc Natl Acad Sci USA 89: 11269–11273

    Article  PubMed  CAS  Google Scholar 

  • Sawa H, Shimura Y (1992) Association of U6 snRNA with the 5’ splice site region of pre-mRNA in the spliceosome. Genes Dev 6: 244–254

    Article  PubMed  CAS  Google Scholar 

  • Schultz J, Jones T, Bork P, Sheer D, Blencke S, Steyrer S, Wellbrock U, Bevec D, Ullrich A, Wallasch C (2001) Molecular characterization of a cDNA encoding functional human CLK4 kinase and localization to chromosome 5q35 [correction of 4q351. Genomics 71: 368–370

    Article  PubMed  CAS  Google Scholar 

  • Screaton GR, Càceres JF, Mayeda A, Bell MV, Plebanski M, Jackson DG, Bell JI, Krainer AR (1995) identification and characterization of three members of the human SR family of pre-mRNA splicing factors. EMBO J 14: 4336–4349

    Google Scholar 

  • Seghezzi W, Chua K, Shanahan F, Gozani O, Reed R, Lees E (1998) Cyclin E associates with components of the pre-mRNA splicing machinery in mammalian cells. Mol Cell Biol 18: 4526–4536

    CAS  Google Scholar 

  • Senger B, Simos G, Bischoff FR, Podtelejnikov A, Mann M, Hurt E (1998) MtrlOp functions as a nuclear import receptor for the mRNA-binding protein Npl3p. EMBO J 17: 2196–2207

    Article  PubMed  CAS  Google Scholar 

  • Séraphin B, Rosbash M (1989) Identification of functional Ul snRNA-pre-mRNA complexes committed to spliceosome assembly and splicing. Cell 59: 349–358

    Article  PubMed  Google Scholar 

  • Shannon K, Guthrie C (1991) Suppressors of a U4 snRNA mutation define a novel U6 snRNP protein with RNA-binding motifs. Genes Dev 5: 773–785

    Article  PubMed  CAS  Google Scholar 

  • Shen J, Zu K, Cass CL, Beyer AL, Hirsh J (1995) Exon skipping by overexpression of a Drosophila heterogeneous nuclear ribonucleoprotein in vivo. Proc Natl Acad Sci USA 92: 1822–1825

    Article  PubMed  CAS  Google Scholar 

  • Siatecka M, Reyes JL, Konarska MM (1999) Functional interactions of Prp8 with both splice sites bat the spliceosomal catalytic center. Genes Dev 13: 1983–1993

    Article  PubMed  CAS  Google Scholar 

  • Siebel CW, Feng L, Guthrie C, Fu XD (1999) Conservation in budding yeast of a kinase specific for SR splicing factors. Proc Natl Acad Sci USA 96: 5440–5445

    Article  PubMed  CAS  Google Scholar 

  • Singh R, Valcarcel J, Green MR (1995) Distinct binding specificities and functions of higher eukaryotic polypyrimidine tract-binding proteins. Science 268: 1173–1176

    Article  PubMed  CAS  Google Scholar 

  • Solary E, Dubrez L, Eymin B, Bertrand R, Pommier Y (1996) Apoptosis of human leukemic cells induced by topoisomerase I and II inhibitors. Bull Cancer (Paris) 83: 205–212

    CAS  Google Scholar 

  • Sontheimer EJ, Steitz JA (1993) The U5 and U6 small nuclear RNAs as active site components of the spliceosome. Science 262: 1989–1996

    Article  PubMed  CAS  Google Scholar 

  • Staley JP, Guthrie C (1999) An RNA switch at the 5’ splice site requires ATP and the DEAD box protein Prp28p. Mol Cell 3: 55–64

    Article  PubMed  CAS  Google Scholar 

  • Steitz JA, Black DL, Gerke V, Parker KA, Krämer A, Frendewey D, Keller W (1988) Functions of the abundant U-snRNPs. In: Birnstiel M (ed) Structure and function of major and minor small nuclear ribonucleoprotein particles. Springer, Berlin Heidelberg New York, pp 115–154

    Chapter  Google Scholar 

  • Stewart AF, Herrera RE, Nordheim A (1990) Rapid induction of c-fos transcription reveals quantitative linkage of RNA polymerase II and DNA topoisomerase I enzyme activities. Cell 60: 141–149

    Article  PubMed  CAS  Google Scholar 

  • Stewart L, Ireton GC, Champoux JJ (1996) The domain organization of human topoisomerase I. J Biol Chem 271: 7602–7608

    Article  PubMed  CAS  Google Scholar 

  • Stojdl DF, Bell JC (1999) SR protein kinases: the splice of life. Biochem Cell Biol 77: 293–298

    Article  PubMed  CAS  Google Scholar 

  • Sun Q, Mayeda A, Hampson RK, Krainer AR, Rottman FM (1993) General splicing factor SF2/ASF promotes alternative splicing by binding to an exonic splicing enhancer. Genes Dev 7: 2598–2608

    Article  PubMed  CAS  Google Scholar 

  • Swanson MS, Dreyfuss G (1988a) Classification and purification of proteins of heterogeneous nuclear ribonucleoprotein particles by RNA binding specificities. Mol Cell Biol 8: 2237–2241

    PubMed  CAS  Google Scholar 

  • Swanson MS, Dreyfuss G (1988b) RNA binding specificity of hnRNP proteins: a subset bind to the 3’ end of introns. EMBO J 7: 3519–3529

    PubMed  CAS  Google Scholar 

  • Tacke R, Manley JL (1999) Determinants of SR protein specificity. Curr Opin Cell Biol 11: 358–362

    Article  PubMed  CAS  Google Scholar 

  • Tacke R, Chen Y, Manley JL (1997) Sequence-specific RNA binding by an SR protein requires RS domain phosphorylation: creation of an SRp40-specific splicing enhancer. Proc Natl Acad Sci USA 94: 1148–1153

    Article  PubMed  CAS  Google Scholar 

  • Takeuchi M, Yanagida M (1993) A mitotic role for a novel fission yeast protein kinase dskl with cell cycle stage dependent phosphorylation and localization. Mol Biol Cell 4: 247–260

    PubMed  CAS  Google Scholar 

  • Tang Z, Kuo T, Shen J, Lin RJ (2000) Biochemical and genetic conservation of fission yeast Dskl and human SR protein-specific kinase 1. Mol Cell Biol 20: 816–824

    Article  PubMed  CAS  Google Scholar 

  • Taylor SJ, Shalloway D (1994) An RNA-binding protein associated with Src through its SH2 and SH3 domains in mitosis. Nature 368: 867–871

    Article  PubMed  CAS  Google Scholar 

  • Tazi J, Daugeron MC, Cathala G, Brunel C, Jeanteur P (1992) Adenosine phosphorothioates ( ATPaS and ATPgS) differentially affect the two steps of mammalian pre-mRNA splicing. J Biol Chem 267: 4322–4326

    Google Scholar 

  • Tazi J, Kornstädt U, Rossi F, Jeanteur P, Cathala G, Brunel C, Luhrmann R (1993) Thiophosphorylation of U1–70K protein inhibits pre-mRNA splicing. Nature 363: 283–286

    Article  PubMed  CAS  Google Scholar 

  • Tazi J, Rossi F, Labourier E, Gallouzi I, Brunel C, Antoine E (1997) DNA topoisomerase I: customs officer at the border between DNA and RNA worlds? J Mol Med 75: 786–800

    Article  PubMed  CAS  Google Scholar 

  • Teigelkamp S, Newman AJ, Beggs JD (1995a) Extensive interactions of PRP8 protein with the 5’ and 3’ splice sites during splicing suggest a role in stabilization of exon alignment by U5 snRNA. EMBO J 14: 2602–2612

    PubMed  CAS  Google Scholar 

  • Teigelkamp S, Whittaker E, Beggs JD (1995b) Interaction of the yeast splicing factor PRP8 with substrate RNA during both steps of splicing. Nucleic Acids Res 23: 320–326

    Article  PubMed  CAS  Google Scholar 

  • Theissen H, Etzerodt M, Reuter R, Schneider C, Lottspeich F, Argos P, Lührmann R, Philipson L (1986) Cloning of the human cDNA for the Ul RNA-associated 70K protein. EMBO J 5: 3209–3217

    PubMed  CAS  Google Scholar 

  • Tsao YP, Russo A, Nyamuswa G, Silber R, Liu LF (1993) Interaction between replication forks and topoisomerase I-DNA cleavable complexes: studies in a cell-free SV40 DNA replication system. Cancer Res 53: 5908–5914

    PubMed  CAS  Google Scholar 

  • Umen JG, Guthrie C (1995a) A novel role for a U5 snRNP protein in 3’ splice site selection. Genes Dev 9: 855–868

    Article  PubMed  CAS  Google Scholar 

  • Umen JG, Guthrie C (1995b) Prp16p, Slu7p, and Prp8p interact with the 3’ splice site in two distinct stages during the second catalytic step of pre-mRNA splicing. RNA 1: 584–597

    PubMed  CAS  Google Scholar 

  • Umen JG, Guthrie C (1995c) The second catalytic step of pre-mRNA splicing. RNA 1: 869–885

    PubMed  CAS  Google Scholar 

  • Urasaki Y, Laco G, Takebayashi Y, Bailly C, Kohlhagen G, Pommier Y (2001) Use of camptothecinresistant mammalian cell lines to evaluate the role of topoisomerase I in the antiproliferative activity of the indolocarbazole, NB-506, and its topoisomerase I binding site. Cancer Res 61: 504–508

    PubMed  CAS  Google Scholar 

  • van der Houven van Oordt W, Diaz-Meco MT, Lozano J, Krainer AR, Moscat J, Caceres JF (2000) The MKK(3/6)-p38-signaling cascade alters the subcellular distribution of hnRNP Al and modulates alternative splicing regulation. J Cell Biol 149: 307–316

    Article  Google Scholar 

  • Wang C, Chua K, Seghezzi W, Lees E, Gozani 0, Reed R (1998) Phosphorylation of spliceosomal protein SAP 155 coupled with splicing catalysis. Genes Dev 12: 1409–1414

    Article  PubMed  CAS  Google Scholar 

  • Wang HY, Lin W, Dyck JA, Yeakley JM, Songyang Z, Cantley LC, Fu XD (1998) SRPK2: a differentially expressed SR protein-specific kinase involved in mediating the interaction and localization of pre-mRNA splicing factors in mammalian cells. J Cell Biol 140: 737–750

    Article  PubMed  CAS  Google Scholar 

  • Wang HY, Arden KC, Bermingham JRJ, Viars CS, Lin W, Boyer AD, Fu XD (1999) Localization of serine kinases, SRPK1 (SFRSK1) and SRPK2 (SFRSK2), specific for the SR family of splicing factors in mouse and human chromosomes. Genomics 57: 310–315

    Article  PubMed  CAS  Google Scholar 

  • Wang J, Manley JL (1995) Overexpression of the SR proteins ASF/SF2 and SC35 influences alternative splicing in vivo in diverse ways. RNA 1: 335–346

    PubMed  CAS  Google Scholar 

  • Wang JC, Lynch AS (1993) Transcription and DNA supercoiling. Curr Opin Genet Dev 3: 764768

    Google Scholar 

  • Wang X, Bruderer S, Rafi Z, Xue J, Milburn PJ, Krämer A, Robinson PJ (1999) Phosphorylation of splicing factor SF1 on Ser20 by cGMP-dependent protein kinase regulates spliceosome assembly. EMBO J 18: 4549–4559

    Article  PubMed  CAS  Google Scholar 

  • Watakabe A, Tanaka K, Shimura Y (1993) The role of exon sequences in splice site selection. Genes Dev 7: 407–418

    Article  PubMed  CAS  Google Scholar 

  • Weg-Remers S, Ponta H, Herrlich P, Konig H (2001) Regulation of alternative pre-mRNA splicing by the ERK MAP-kinase pathway. EMBO J 20: 4194–4203

    Article  PubMed  CAS  Google Scholar 

  • Weighardt F, Biamonti G, Riva S (1995) Nucleo-cytoplasmic distribution of human hnRNP proteins: a search for the targeting domains in hnRNP Al. J Cell Sci 108: 545–555

    PubMed  CAS  Google Scholar 

  • Wilusz J, Shenk T (1990) A uridylate tract mediates efficient heterogeneous nuclear ribonucleoprotein C protein-RNA cross-linking and functionally substitutes for the downstream element of the polyadenylation signal. Mol Cell Biol 10: 6397–6407

    PubMed  CAS  Google Scholar 

  • Wilusz J, Feig DI, Shenk T (1988) The C proteins of heterogeneous nuclear ribonucleoprotein complexes interact with RNA sequences downstream of polyadenylation cleavage sites. Mol Cell Biol 8: 4477–4483

    PubMed  CAS  Google Scholar 

  • Woppmann A, Will CL, Konstädt U, Zuo P, Manley JM, Lührmann R (1993) Identification of an snRNP-associated kinase activity that phosphorylates arginine/serine-rich domains typical of splicing factors. Nucleic Acids Res 21: 2815–2822

    Article  PubMed  CAS  Google Scholar 

  • Wu JY, Maniatis T (1993) Specific interactions between proteins implicated in splice site selection and regulated alternative splicing. Cell 75: 1061–1070

    Article  PubMed  CAS  Google Scholar 

  • Wu S, Romfo CM, Nilsen TW, Green MR (1999) Functional recognition of the 3’ splice site AG by the splicing factor U2AF35. Nature 402: 832–835

    Article  PubMed  CAS  Google Scholar 

  • Wyatt J, Sontheimer EJ, Steitz JA (1992) Site-specific cross-linking of mammalian U5 snRNP to the 5’ splice site before the first step of pre-mRNA splicing. Genes Dev 6: 2542–2553

    Article  PubMed  CAS  Google Scholar 

  • Xiao SH, Manley JL (1997) Phosphorylation of the ASF/SF2 RS domain affects both proteinprotein and protein-RNA interactions and is necessary for splicing. Genes Dev 11: 334–344

    Article  PubMed  CAS  Google Scholar 

  • Xiao SH, Manley JL (1998) Phosphorylation-dephosphorylation differentially affects activities of splicing factor ASF/SF2. EMBO J 17: 6359–6367

    Article  PubMed  CAS  Google Scholar 

  • Yang X, Bani MR, Lu SJ, Rowan S, Ben-David Y, Chabot B (1994) The Al and Alb proteins of heterogeneous nuclear ribonucleoparticles modulate 5’ splice site selection in vivo. Proc Natl Acad Sci USA 91: 6924–6928

    Article  PubMed  CAS  Google Scholar 

  • Yeakley JM, Tronchere H, Olesen J, Dyck JA, Wang HY, Fu XD (1999) Phosphorylation regulates in vivo interaction and molecular targeting of serine/arginine-rich pre-mRNA splicing factors. J Cell Biol 145: 447–455

    Article  PubMed  CAS  Google Scholar 

  • Yoshinari T, Matsumoto M, Arakawa H, Okada H, Noguchi K, Suda H, Okura A, Nishimura S (1995) Novel antitumor indolocarbazole compound 6-N-formylamino-12,13-dihydro-1,11dihydroxy-13 -(beta-D-glucopyranosyl)-5H-indolo [2,3 -a] pyrrolo [3,4-c] carbazole-5, 7 (6H) -dione (NB-506): induction of topoisomerase I-mediated DNA cleavage and mechanisms of cell line-selective cytotoxicity. Cancer Res 55: 1310–1315

    CAS  Google Scholar 

  • Yun B, Farkas R, Lee K, Rabinow L (1994) The Doa locus encodes a member of a new protein kinase family and is essential for eye and embryonic development in Drosophila melanogaster. Genes Dev 8: 1160–1173

    Article  PubMed  CAS  Google Scholar 

  • Yun B, Lee K, Farkas R, Hitte C, Rabinow L (2000) The LAMMER protein kinase encoded by the Doa locus of Drosophila is required in both somatic and germline cells and is expressed as both nuclear and cytoplasmic isoforms throughout development. Genetics 156: 749–761

    PubMed  CAS  Google Scholar 

  • Zahler AM, Lane WS, Stolk JA, Roth MB (1992) SR proteins: a conserved family of pre-mRNA splicing factors. Genes Dev 6: 837–847

    Article  PubMed  CAS  Google Scholar 

  • Zahler AM, Neugebauer KM, Lane WS, Roth MB (1993) Distinct functions of SR proteins in alternative pre-mRNA splicing. Science 260: 219–222

    Article  PubMed  CAS  Google Scholar 

  • Zamore PD, Green MR (1989) Identification, purification, and biochemical characterization of U2 small nuclear ribonucleoprotein auxiliary factor. Proc Natl Acad Sci USA 86: 9243–9247

    Article  PubMed  CAS  Google Scholar 

  • Zamore PD, Green MR (1991) Biochemical characterization of U2 snRNP auxiliary factor: an essential pre-mRNA splicing factor with a novel intranuclear distribution. EMBO J 10: 207–214

    PubMed  CAS  Google Scholar 

  • Zamore PD, Patton JG, Green MR (1992) Cloning and domain structure of the mammalian splicing factor U2AF. Nature 335: 609–614

    Article  Google Scholar 

  • Zhang H, Wang JC, Liu LF (1988) Involvement of DNA topoisomerase I in the transcription of human ribosomal RNA genes. Cell 85: 1060–1064

    CAS  Google Scholar 

  • Zhang M, Zamore PD, Carmo-Fonseca M, Lamond AI, Green MR (1992) Cloning and intracellular localization of the U2 small nuclear ribonucleoprotein auxiliary factor small subunit. Proc Natl Acad Sci USA 89: 8769–8773

    Article  PubMed  CAS  Google Scholar 

  • Zhu J, Krainer AR (2000) Pre-mRNA splicing in the absence of an SR protein RS domain. Genes Dev 14: 3166–3178

    Article  PubMed  CAS  Google Scholar 

  • Zhu J, Mayeda A, Krainer AR (2001) Exon identity established through differential antagonism between exonic splicing silencer-bound hnRNP Al and enhancer-bound SR proteins. Mol Cell 8: 1351–1361

    Article  PubMed  CAS  Google Scholar 

  • Zhuang Y, Weiner AM (1986) A compensatory base change in Ul snRNA suppresses a 5’ splice site mutation. Cell 46: 827–835

    Article  PubMed  CAS  Google Scholar 

  • Zorio DA, Blumenthal T (1999) Both subunits of U2AF recognize the 3’ splice site in Caenorhabditis elegans. Nature 402: 835–838

    Article  PubMed  CAS  Google Scholar 

  • Zuo P, Maniatis T (1996) The splicing factor U2AF35 mediates critical protein-protein interactions in constitutive and enhancer-dependent splicing. Genes Dev 10: 1356–1368

    Article  PubMed  CAS  Google Scholar 

  • Zuo P, Manley JL (1993) Functional domains of the human splicing factor ASF/SF2. EMBO J 12: 4727–4737

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institut de Génétique Moléculaire, UMR5535 du CNRS, IFR 24, 1919 Route de Mende, 34293, Montpellier Cedex 5, France

    J. Tazi

Authors
  1. J. Soret
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. Tazi
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Institute of Molecular Genetics of Montpellier, CNRS, 1919 Route de Mende, BP 5051, 34293, Montpellier Cedex 05, France

    Philippe Jeanteur

Rights and permissions

Reprints and permissions

Copyright information

© 2003 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Soret, J., Tazi, J. (2003). Phosphorylation-Dependent Control of the Pre-mRNA Splicing Machinery. In: Jeanteur, P. (eds) Regulation of Alternative Splicing. Progress in Molecular and Subcellular Biology, vol 31. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-09728-1_4

Download citation

  • DOI: https://doi.org/10.1007/978-3-662-09728-1_4

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-07858-3

  • Online ISBN: 978-3-662-09728-1

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation