Skip to main content
SpringerLink
Log in

Alternative Pre-mRNA Splicing and Regulation of Programmed Cell Death

  • Chapter
Regulation of Alternative Splicing

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

Abstract

Apoptosis or programmed cell death (PCD) is critical for development and homeostasis of multi-cellular organisms. It also plays an important role in pathogenesis of a large number of human diseases. PCD is under complex regulation at multiple levels. An important level of this regulation is at the level of pre-mRNA splicing because a number of PCD regulatory genes are expressed as functionally distinct or even antagonistic isoforms as a result of alternative splicing. In this chapter, we review recent molecular and biochemical studies on alternative splicing of these PCD genes, ranging from extra-cellular signals, death receptors to intracellular components of the death machinery. As a major mechanism to generate transcript variability, alternative splicing affects not only intracellular distribution, but also functional activities of these PCD genes, modulating a presumably tightly controlled process of cell death. In some cases, alternative splicing is involved in the life-or-death decision. Studies with molecular and biochemical approaches have begun to reveal mechanisms underlying alternative splicing regulation of PCD gene expression and function. Many important questions remain to be addressed by future studies.

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

  • Alnemri ES (1997) Mammalian cell death proteases: a family of highly conserved aspartate specific cysteine proteases. J Cell Biochem 64: 33–42

    PubMed  CAS  Google Scholar 

  • Alnemri ES, Fernandes-Alnemri T, Litwack G (1995) Expression of four novel isoforms of human interleukin- 1 converting enzyme with different apoptotic activities. J Biol Chem 270: 4312–4317

    PubMed  CAS  Google Scholar 

  • Alnemri ES, Livingston DJ, Nicholson DW, Salvesen G, Thornberry NA, Wong WW, Yuan J (1996) Human ICE/CED-3 protease nomenclature. Cell 87: 171

    PubMed  CAS  Google Scholar 

  • Al-Zoubi AM, Efimova EV, Kaithamana S, Martinez 0, El-Idrissi Mel-A, Dogan RE, Prabhakar BS (2001) Contrasting effects of IG20 and its splice isoforms, MADD and DENN-SV, on tumor necrosis factor alpha-induced apoptosis and activation of caspase-8 and -3. J Biol Chem 276: 47202–47211

    PubMed  CAS  Google Scholar 

  • Aravind L, Dixit VM, Koonin EV (1999) The domains of death: evolution of the apoptosis machinery. Trends Biochem Sci 24 (2): 47–53

    PubMed  CAS  Google Scholar 

  • Aravind L, Dixit VM, Koonin EV (2001) Apoptotic molecular machinery: vastly increased complexity in vertebrates revealed by genome comparisons. Science 291 (5507): 1279–1284

    PubMed  CAS  Google Scholar 

  • Ashhab Y, Alian A, Polliack A, Panet A, Yehuda DB (2001) Two splicing variants of a new inhibitor of apoptosis gene with different biological properties and tissue distribution pattern. FEBS Lett 495 (1–2): 56–60

    PubMed  CAS  Google Scholar 

  • Atamas SP (1997) Alternative splice variants of cytokines: making a list. Life Sci 61 (12): 1105–1112

    PubMed  CAS  Google Scholar 

  • Bae J, Leo CP, Hsu SY, Hsueh AJW (2000) Mcl-1S, a splicing variant of the antiapoptotic bd-2 family member Mcl-1, encodes a proapoptotic protein possessing only the BH3 domain. J Biol Chem 275: 25255–25261

    PubMed  CAS  Google Scholar 

  • Balvay L, Libri D, Gallego M, Fiszman MY (1992) Intronic sequence with both negative and positive effects on the regulation of alternative transcripts of the chicken beta tropomyosin transcripts._Nucleic Acids Res 20: 3987–3992

    CAS  Google Scholar 

  • Benedict MA, Hu Y, Inohara N, Nunez G (2000) Expression and functional analysis of Apaf-1 isoforms. Extra Wd-40 repeat is required for cytochrome c binding and regulated activation of procaspase-9. J Biol Chem 275 (12): 8461–8468

    PubMed  CAS  Google Scholar 

  • Berget SM (1995) Exon recognition in vertebrate splicing. J Biol Chem 2: 2411–2414

    Google Scholar 

  • Bertin J, DiStefano PS (2000) The PYRIN domain: a novel motif found in apoptosis and inflammation proteins. Cell Death Differ 7 (12): 1273–1274

    PubMed  CAS  Google Scholar 

  • Black DL (1995) Finding splice sites within a wilderness of RNA. RNA 1: 763–771

    PubMed  CAS  Google Scholar 

  • Blanchette M, Chabot B(1999) Modulation of exon skipping by high affinity hnRNP Al binding sites and by intron elements that repress splice site utilisation. EMBO J 18: 1939–1952

    Google Scholar 

  • Blencowe BJ (2000) Exonic splicing enhancers: mechanism of action, diversity and role in human genetic diseases. Trends Biochem Sci 25 (3): 106–110

    PubMed  CAS  Google Scholar 

  • Boise LH, Gonzalez-Garcia M, Postema CE, Ding L, Lindsten T, Turka LA, Mao X, Ntifez G, Thompson CB (1993) bd-x, a bc1–2-related gene that functions as a dominant regulator of apoptotic cell death. Cell 74: 597–608

    Google Scholar 

  • Boucher L, Ouzounis CA, Enright AJ, Blencowe BJ (2001) A genome-wide survey of RS domain proteins. RNA 7 (12): 1693–1701

    PubMed  CAS  Google Scholar 

  • Bourgeois CF, Popielarz M, Hildwein G, Stevenin J (1999) Mol Cell Biol 19: 7347–7356

    PubMed  CAS  Google Scholar 

  • Brink R, Lodish HF (1998) Tumor necrosis factor receptor (TNFR)-associated factor 2A (TRAF2A), a TRAF2 splice variant with an extended RING finger domain that inhibits TNFR2-mediated NF-kappaB activation. J Biol Chem 273 (7): 4129–4134

    PubMed  CAS  Google Scholar 

  • Carlo T, Sterner DA, Berget SM (1996) RNA 2: 342–353

    PubMed  CAS  Google Scholar 

  • Carstens RP, McKeehan WL, Garcia-Blanco MA (1998) An intronic sequence element mediates both activation and repression of rat fibroblast growth factor receptor 2 pre-mRNA splicing. Mol Cell Biol 18: 2205–2217

    PubMed  CAS  Google Scholar 

  • Cascino I, Fiucci G, Papoff G, Ruberti G (1995) Three functional soluble forms of the human apoptosis-inducing Fas molecule are produced by alternative splicing. J Immunol 154: 2706–2713

    PubMed  CAS  Google Scholar 

  • Cascino I, Papoff G, Maria D, Testi R, Ruberti G (1996) Fas/Apo-1/CD95 receptor lacking the intracytoplasmic signaling domain protects tumor cells from Fas-mediated apoptosis. J Immunol 156: 13

    PubMed  CAS  Google Scholar 

  • Chabot B (1996) Directing alternative splicing: cast and scenarios. Trends Genet 12(11): 472478

    Google Scholar 

  • Chan RC, Black DL (1995) Conserved intron elements repress splicing of a neuron-specific c-src exon in vitro. Mol Cell Biol 15: 6377–6385

    PubMed  CAS  Google Scholar 

  • Cheng J, Zhou T, Liu C, Shapiro JP, Brauer MJ, Kiefer MC, Barr PJ, Mountz JD (1994) Protection from Fas-mediated apoptosis by a soluble form of the Fas molecule. Science 263: 1759

    PubMed  CAS  Google Scholar 

  • Chew SL, Baginsky L, Eperon IC (2000) An exonic splicing silencer in the testes DNA specific DNA ligase III beta exon. Nucleic Acids Res 28: 402–410

    PubMed  CAS  Google Scholar 

  • Chou MY, Rooke N, Turck CW, Black DL (1999) hnRNP H is a component of a splicing enhancer complex that activates a c-src alternative exon in neuronal cells. Mol Cell Biol 19: 69–77

    Google Scholar 

  • Chinnaiyan AM, O’Rourke K, Lane BR, Dixit VM (1997) Interaction of CED-4 with CED-3 and

    Google Scholar 

  • CED-9: a molecular framework for cell death. Science 275:1122–1126

    Google Scholar 

  • Clary DO, Reichardt LF (1994) An alternatively spliced form of the nerve growth factor receptor TrkA confers an enhanced response to neurotrophin 3. Proc Natl Acad Sci USA 91 (23): 11133–11137

    PubMed  CAS  Google Scholar 

  • Conway EM, Pollefeyt S, Cornelissen J, DeBaere I, Steiner-Mosonyi M, Ong K, Baens M, Collen D, Schuh AC (2000) Three differentially expressed survivin cDNA variants encode proteins with distinct antiapoptotic functions. Blood 95 (4): 1435–1442

    PubMed  CAS  Google Scholar 

  • Cooper TA, Mattox W (1997) The regulation of splice-site selection, and its role in human disease. Am J Hum Genet 61 (2): 259–266

    PubMed  CAS  Google Scholar 

  • Cote J, Simard MJ, Chabot B (1999) An element in the 5’ common exon of the NCAM alternative splicing unit interacts with SR proteins and modulates 5’ splice site selection. Nucleic Acids Res 27 (12): 2529–2537

    PubMed  CAS  Google Scholar 

  • Cote J, Dupuis S, Jiang Z, Wu JY (2001a) Caspase-2 pre-mRNA alternative splicing: Identification of an intronic element containing a decoy 3’ acceptor site. Proc Natl Acad Sci USA 98 (3): 938–943

    PubMed  CAS  Google Scholar 

  • Cote J, Dupuis S, Wu JY (200 lb) Polypyrimidine track-binding protein binding downstream of caspase-2 alternative exon 9 represses its inclusion. J Biol Chem 276(11):8535–8543

    Google Scholar 

  • Curtis D, Lehmann R, Zamore PD (1995) Translational regulation in development. Cell 81: 171–178

    PubMed  CAS  Google Scholar 

  • Del Gatto F, Breathnach R(1995) Exon and intron sequences, respectively, repress and activate splicing of a fibroblast growth factor receptor 2 alternative exon. Mol Cell Biol 15: 4825–4834

    Google Scholar 

  • Donnini M, Lapucci A, Papucci L, Witort E, Tempestini A, Brewer G, Bevilacqua A, Nicolin A, Capaccioli S, Schiavone N (2001) Apoptosis is associated with modifications of bd-2 mRNA AU-binding proteins. Biochem Biophys Res Commun 287 (5): 1063–1069

    PubMed  CAS  Google Scholar 

  • Dredge BK, Polydorides AD, Darnell RB (2001) The splice of life: alternative splicing and neurological disease. Nat Rev Neurosci 2 (1): 43–50

    PubMed  CAS  Google Scholar 

  • Du X, Poltorak A, Wei Y, Beutler B (2000) Three novel mammalian toll-like receptors: gene structure, expression, and evolution. Eur Cytokine Netw 11 (3): 362–371

    PubMed  CAS  Google Scholar 

  • Elrick LL, Humphrey MB, Cooper TA, Berget SM (1998) Mol Cell Biol 18: 343–352

    PubMed  CAS  Google Scholar 

  • Fang W, Rivard JJ, Mueller DL, Behrens TW (1994) Cloning and molecular characterization of mouse bcl-x in B and T lymphocytes. J Immunol 153 (10): 4388–4398

    PubMed  CAS  Google Scholar 

  • Fernandes-Alnemri T, Litwack G, Alnemri ES (1995a) Mch2, a new member of the apoptotic Ced-3/Ice cysteine protease gene family. Cancer Res 55 (13): 2737–2742

    PubMed  CAS  Google Scholar 

  • Fernandes-Alnemri T, Takahashi A, Armstrong R, Krebs J, Fritz L, Tomaselli KJ, Wang L, Yu Z, Croce CM, Salveson G et al. (1995b) Mch3, a novel human apoptotic cysteine protease highly related to CPP32.Cancer Res 55 (24): 6045–6052

    CAS  Google Scholar 

  • Fesik SW (2000) Insights into programmed cell death through structural biology. Cell 103 (2): 273–282

    PubMed  CAS  Google Scholar 

  • Förch P, Valcarcel J (2001) Molecular mechanisms of gene expression regulation by the apoptosis-promoting protein TIA-1. Apoptosis 6 (6): 463–468

    PubMed  Google Scholar 

  • Förch P, Puig 0, Kedersha N, Martinez C, Granneman S, Seraphin B, Anderson P, Valcarcel J (2000) The apoptosis-promoting factor TIA-1 is a regulator of alternative pre-mRNA splicing. Mol Cell 6 (5): 1089–1098

    PubMed  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Gallego ME, Gattoni R, Stevenin J, Marie J, Expert-Bezancon A (1997) The SR splicing factors

    Google Scholar 

  • ASF/SF2 and SC35 have antagonistic effects on intronic enhancer-dependent splicing of the

    Google Scholar 

  • beta tropomyosin alternative exon. EMBO J 16:1772–1784

    Google Scholar 

  • Gamper C, Omene CO, van Eyndhoven WG, Glassman GD, Lederman S (2001) Expression and function of TRAF-3 splice-variant isoforms in human lymphoma cell lines. Hum Immunol 62 (10): 1167–1177

    PubMed  CAS  Google Scholar 

  • Gibson L, Holmgreen SP, Huang DCS, Bernard 0, Copeland NG, Jenkins NA, Sutherland GR, Baker E, Adams JM, Cory S (1996) Bd-w, a novel member of the bd-2 family, promotes cell survival. Oncogene 13: 665–675

    PubMed  CAS  Google Scholar 

  • Gleichmann M, Gillen C, Czardybon M, Bosse F, Greiner-Petter R, Auer J, Muller HW (2000) Cloning and characterization of SDF-lgamma, a novel SDF-1 chemokine transcript with developmentally regulated expression in the nervous system. Eur J Neurosci 12(6): 18571866

    Google Scholar 

  • Goldstrohm AC, Greenleaf AL, Garcia-Blanco MA (2001) Co-transcriptional splicing of pre-messenger RNAs: considerations for the mechanism of alternative splicing. Gene 277 (1–2): 31–47

    PubMed  CAS  Google Scholar 

  • Gontarek RR, McNally MT, Beemon K (1993) Genes Dev 7: 1926–1936

    PubMed  CAS  Google Scholar 

  • Gonzalez-Garcia M, Perez-Ballestero R, Ding LY Duan L, Boise LH, Thompson CB, Nunez G (1994) Bc1-xL is the major bd-x mRNA form expressed during murine development and its product localizes to mitochondria. Development 120: 3033–3042

    PubMed  CAS  Google Scholar 

  • Grabowski PJ, Black DL (2001) Alternative RNA splicing in the nervous system. Prog Neurobiol 65: 289–308

    PubMed  CAS  Google Scholar 

  • Grillot DAM, Gonzalez-Garcia M, Ekhterae D, Duan L, Inohara N, Ohta S, Seldin MF, and Nunez G (1997) Genomic organization, promoter region analysis, and chromosome localization of the mouse bd-x gene. J Immunol 158: 4750–4757

    PubMed  CAS  Google Scholar 

  • Hastings ML, Krainer AR (2001) Pre-mRNA splicing in the new millennium. Curr Opin Cell Biol 13 (3): 302–309

    PubMed  CAS  Google Scholar 

  • Hardiman G, Rock FL, Balasubramanian S, Kastelein RA, Bazan JF (1996) Molecular characterization and modular analysis of human MyD88. Oncogene 13 (11): 2467–2475

    PubMed  CAS  Google Scholar 

  • Haut DD, Pintel DJ (1999) Inclusion of the NS2 specific exon in minute virus of mice mRNA is facilitated by an intronic splicing enhancer that affects definition of the downstream small intron. Virology 258: 84–94

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Hockenbery D, Nunez G, Milliman C, Schreiber RD, Korsmeyer SJ (1990) Bd-2 is an inner mitochondria) membrane protein that blocks programmed cell death. Nature 348: 334–336

    PubMed  CAS  Google Scholar 

  • Horiuchi T, Himeji D, Tsukamoto H, Harashima S, Hashimura C, Hayashi K (2000) Dominant expression of a novel splice variant of caspase-8 in human peripheral blood lymphocytes. Biochem Biophys Res Commun 272 (3): 877–881

    PubMed  CAS  Google Scholar 

  • Horvitz HR (1999) Genetic control of programmed cell death in the nematode Caenorhabditis elegans. Cancer Res 59 (7 Suppl): 1701s - 1706s

    PubMed  CAS  Google Scholar 

  • Horvitz HR, Shaham S, Hengartner MO (1994) The genetics of programmed cell death in the nematode caenorhabditis elegans. Cold Spring Harb Symp Quat Bio159: 377–385

    Google Scholar 

  • Huang Y, Shin NH, Sun Y, Wang KK (2001) Molecular cloning and characterization of a novel caspase-3 variant that attenuates apoptosis induced by proteasome inhibition. Biochem Biophys Res Commun 18283 (4): 762–769

    Google Scholar 

  • Huh GS, Hynes RO (1994) Regulation of alternative pre-mRNA splicing by a novel repeated hexanucleotide element. Genes Dev 8: 1561–1574

    PubMed  CAS  Google Scholar 

  • Humphrey MB, Bryan J, Cooper TA, Berget SM (1995) A 32-nucleotide exon-splicing enhancer regulates usage of competing 5’ splice sites in a differential internal exon. Mol Cell Biol 15: 3979–3988

    PubMed  CAS  Google Scholar 

  • Ito A, Uehara T, Nomura Y (2000). Isolation of Ich-1 S (caspase-2 S)-binding protein that partially inhibits caspase activity. FEBS Lett 470: 360–364

    PubMed  CAS  Google Scholar 

  • Iwami KI, Matsuguchi T, Masuda A, Kikuchi T, Musikacharoen T, Yoshikai Y (2000) Cutting edge: naturally occurring soluble form of mouse Toll-like receptor 4 inhibits lipopolysaccharide signaling. J Immunol 165 (12): 6682–6686

    PubMed  CAS  Google Scholar 

  • Jacobson MD, Weil M, Raff MC (1997) Programmed cell death in animal development. Cell 88: 347–354

    PubMed  CAS  Google Scholar 

  • Jensen LE, Whitehead AS (2001) IRAK1b, a novel alternative splice variant of interleukin-1 receptor-associated kinase (IRAK), mediates interleukin-1 signaling and has prolonged stability. J Biol Chem 276 (31): 29037–29044

    PubMed  CAS  Google Scholar 

  • Jiang ZH, Wu JY (1999) Alternative splicing and programmed cell death. Proc Soc Exp Biol Med 220 (2): 64–72

    PubMed  CAS  Google Scholar 

  • 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): 9155–9160

    PubMed  CAS  Google Scholar 

  • Jiang W, Kumar JM, Matters GL, Bond JS (2000) Structure of the mouse metalloprotease meprin beta gene (Meplb): alternative splicing in cancer cells. Gene 248 (1–2): 77–87

    PubMed  CAS  Google Scholar 

  • Jin W, Huang ES, Bi W, Cote GJ (1999) Redundant intronic repressor function to inhibit fibroblast growth factor receptor one alpha exon recognition in glioblastoma cells. J Biol Chem 274: 28035–28041

    PubMed  CAS  Google Scholar 

  • Kanopka A, Mühlemann O, Aküsjarvi G (1996) Inhibition by SR proteins of splicing of a regulated adenovirus pre-mRNA. Nature 381: 535–538

    PubMed  CAS  Google Scholar 

  • Kanuka H, Sawamoto K, Inokara N, Matsuno K, Okano H, Mirra H (1999) Control of the cell death pathway by Dapaf-1, a Drosophila Apaf-1/CED 4-related caspase activation. Mol Cell 4: 757769

    Google Scholar 

  • Keene JD (2001) Ribonucleoprotein infrastructure regulating the flow of genetic information between the genome and the proteome. Proc Natl Acad Sci USA 98 (13): 7018–7024

    PubMed  CAS  Google Scholar 

  • Kerr JF, Wyllie AH, Currie AR (1972) Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 26: 239–257

    PubMed  CAS  Google Scholar 

  • Konarska MM (1998) Recognition of the 5’ splice site by the spliceosome. Acta Biochim Pol 45 (4): 869–881

    PubMed  CAS  Google Scholar 

  • Korsmeyer SJ, Gross A, Harada H, Zha J, Wang K, Yin XM, Wei M, Zinkel S (1999) Death and survival signals determine active/inactive conformations of pro-apoptotic BAX, BAD, and BID molecules. Cold Spring Harbor Symp Quant Biol 64: 343–350

    Google Scholar 

  • Korte A, Kochling J, Badiali L, Eckert C, Andreae J, Geilen W, Kebelmann-Betzing C, Taube T, Wu S, Henze G, Seeger K (2000) Expression analysis and characterization of alternatively spliced transcripts of human IL-7Ralpha chain encoding two truncated receptor proteins in relapsed childhood ALL. Cytokine 12 (11): 1597–1608

    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

    PubMed  Google Scholar 

  • Ladner MB, Martin GA, Noble JA, Nikoloff DM, Tal R (1987) Human CSF-1: gene structure and alternative splicing of mRNA precursors. EMBO J 6: 2693–2698

    PubMed  CAS  Google Scholar 

  • Lavigueur A, La Branche H, Kornblihtt AR, Chabot B (1993) A splicing enhancer in the human fibronectin alternate ED1 exon interacts with SR proteins and stimulates U2 snRNP binding. Genes Dev 7: 2405–2417

    PubMed  CAS  Google Scholar 

  • Liu X, Li P, Widlak P, Zou H, Luo X, Garrard WT, Wang X (1998) The 40-kDa subunit of DNA fragmentation factor induces DNA fragmentation and chromatin condensation during apoptosis. Proc Natl Acad Sci USA 95 (15): 8461–8466

    PubMed  CAS  Google Scholar 

  • Lou H, Yang Y, Cote GJ, Berget SM, Gagel RF (1995) An intron enhancer of a 5’ splice site sequence in the human calcitonin/ CGRP gene. Mol Cell Biol 15: 7135–7142

    PubMed  CAS  Google Scholar 

  • Masuoka J, Shiraishi T, Ichinose M, Mineta T, Tabuchi K (2001) Expression of ICAD-1 and ICADS in human brain tumor and its cleavage upon activation of apoptosis by anti-Fas antibody. Jpn J Cancer Res 92 (7): 806–812

    PubMed  CAS  Google Scholar 

  • McCullough AJ, Berget SM (1997) G triplets located throughout clss of small vertebrate introns enforce intron borders and regulate splice site selection. Mol Cell Biol 17: 45624571

    Google Scholar 

  • Milbrandt J, de Sauvage FJ, Fahrner TJ, Baloh RH, Leitner ML, Tansey MG, Lampe PA, Heuckeroth RO, Kotzbauer PT, Simburger KS, Golden JP, Davies JA, Vej sada R, Kato AC, Hynes M, Sherman D, Nishimura M, Wang LC, Vandlen R, Moffat B, Klein RD, Poulsen K, Gray C, Garces A, Johnson EM Jr et al. (1998) Persephin, a novel neurotrophic factor related to GDNF and neurturin. Neuron 20 (2): 245–253

    PubMed  CAS  Google Scholar 

  • Min H, Chan RC, Black DL (1995) The generally expressed hnRNP F is involved in a neural-specific pre-mRNA splicing event. Genes Dev 9: 2659–2671

    PubMed  CAS  Google Scholar 

  • Min H, Turck CW, Nikolic JM, Black DL (1997) Genes Dev 11: 1023–1036

    PubMed  CAS  Google Scholar 

  • Muro AF, Caputi M, Pariyarath R, Pagani, F, Buratti E, Baralle FE (1999) Regulation of fibronectin EDA exon alternative splicing; possible role of RNA secondary structure for enhancer display. Mol Cell Biol 19: 2657–2671

    PubMed  CAS  Google Scholar 

  • Miyashita T, Shikama Y, Tadokoro K, Yamada M (2001) Molecular cloning and characterization of six novel isoforms of human Bim, a member of the proapoptotic Bd-2 family FEBS Lett 509 (1): 135–141

    Google Scholar 

  • Moore JM, Query CC, Sharp PA (1993) Splicing of precursor to messenger RNAs by the spliceosome. In: Gesteland RF, Atkins JF (eds) The RNA world. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, pp 303–358

    Google Scholar 

  • Motoyama N, Wang F, Roth KA, Sawa H, Nakayama KI et al. (1995) Massive cell death of immature hematopoietic cells and neurons in Bd-x deficient mice. Science 267: 1506–1510

    PubMed  CAS  Google Scholar 

  • Manley JL, Tacke R (1996) SR proteins and splicing control. Genes Dev 10 (13): 1569–1579

    PubMed  CAS  Google Scholar 

  • Nakano K, Vousden KH (2001) PUMA, a novel proapoptotic gene, is induced by p53. Mol Cell 7 (3): 683–694

    PubMed  CAS  Google Scholar 

  • Nicholson DW, Thornberry NA (1997) Caspases: killer proteases. Trends Biochem Sci 22: 299306

    Google Scholar 

  • Nijhawan D, Honarpour N, Wang X (2000) Apoptosis in neural development and disease. Annu Rev Neurosci 23: 73–87

    PubMed  CAS  Google Scholar 

  • Nunez G, Benedict MA, Hu Y, Inohara N (1998) Caspases: the proteases of the apoptotic pathway. Oncogene 17 (25): 3237–3245

    PubMed  Google Scholar 

  • O’Connor L, Strasser A, O’ Reilly LA, Hausmann G, Adams JM, Cory S, Huang DCS (1998) Bim: a novel member of the Bd-2 family that promotes apoptosis. EMBO J 17: 384–395

    PubMed  Google Scholar 

  • Oltvai ZN, Milliman CL, Korsmeyer SJ (1993) Bd-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell 74: 609–619

    Google Scholar 

  • Pan G, O’Rourke K, Chinnaiyan AM, Gentz R, Ebner R, Ni J, Dixit VM (1997) The receptor for the cytotoxic ligand TRAIL. Science 276: 111–113

    PubMed  CAS  Google Scholar 

  • Papin S, Duquesnoy P, Cazeneuve C, Pantel J, Coppey-Moisan M, Dargemont C, Amselem S (2000) Alternative splicing at the MEFV locus involved in familial Mediterranean fever regulates translocation of the marenostrin/pyrin protein to the nucleus. Human Mol Genet 9 (20): 3001–3009

    CAS  Google Scholar 

  • Papoff G, Cascino I, Eramo A, Starace G, Lynch DH, Ruberti G (1996) An N-terminal domain shared by Fas/Apo-1 (CD95) soluble variants prevents cell death in vitro. J Immunol 156 (12): 4622–4630

    PubMed  CAS  Google Scholar 

  • Philips AV, Cooper TA (2000) RNA processing and human disease. Cell Mol Life Sc 57 (2): 235–249

    CAS  Google Scholar 

  • Pret AM, Balvay L, Fiszman MY (1999) Regulated splicing of an alternative exon of betatropomyosin pre-mRNA s in myogenic cells depends on the strength of pyrimidine-rich intronic enhancer elements. DNA Cell Biol 18: 671–683

    PubMed  CAS  Google Scholar 

  • Puttaraju M, DiPasquale J, Baker CC, Mitchell LG, Garcia-Blanco MA (2001) Messenger RNA repair and restoration of protein function by spliceosome-mediated RNA trans-splicing. Mol Ther 4 (2): 105–114

    PubMed  CAS  Google Scholar 

  • Rasper DM, Vaillancourt JP, Hadano S, Houtzager VM, Seiden I, Keen SL, Tawa P, Xanthoudakis S, Nasir J, Martindale D, Koop BF, Peterson EP, Thornberry NA, Huang J, MacPherson DP, Black SC, Hornung F, Lenardo MJ, Hayden MR, Roy S, Nicholson DW (1998) Cell death attenuation by `Usurpin’, a mammalian DED-caspase homologue that precludes caspase-8 recruitment and activation by the CD-95 (Fas, APO-1) receptor complex. Cell Death Differ 5(4): 271288

    Google Scholar 

  • Rathmell JC, Thompson CB (1999) The central effectors of cell death in the immune system. Annu Rev Immunol 17: 781–828

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Robinson CJ, Stringer SE (2001) The splice variants of vascular endothelial growth factor (VEGF) and their receptors. J Cell Sci 114 (Pt 5): 853–865

    PubMed  CAS  Google Scholar 

  • Ruberti G, Cascino I, Papoff G, Eramo A (1996) Fas splicing variants and their effect on apoptosis. Adv Exp Med Biol 406: 125–134

    PubMed  CAS  Google Scholar 

  • Ryan KJ, Cooper TA (1996) Mol Cell Biol 16: 4014–4023

    PubMed  CAS  Google Scholar 

  • Samejima K, Earnshaw WC (2000) Differential localization of ICAD-L and ICAD-S in cells due to removal of a C-terminal NLS from ICAD-L by alternative splicing. Exp Cell Res 255(2): 314320

    Google Scholar 

  • Schiavone N, Rosini P, Quattrone A, Donnini M, Lapucci A, Citti L, Bevilacqua A, Nicolin A, Capaccioli S (2000) A conserved AU-rich element in the 3’ untranslated region of bd-2 mRNA is endowed with a destabilizing function that is involved in bc1–2 down-regulation during apoptosis. FASEB J 14 (1): 174–184

    CAS  Google Scholar 

  • Screaton GR, Xu XN, Olsen AL, Cowper AE, Tan R, McMichael AJ, Bell JI (1997a) LARD: a new lymphoid-specific death domain containing receptor regulated by alternative pre-mRNA splicing. Proc Natl Acad Sci USA 94: 4615–4619

    PubMed  CAS  Google Scholar 

  • Screaton GR, Mongkolsapaya J, Xu XN, Cowper AE, McMichael AJ, Bell JI (1997b) TRICK2, a new alternatively spliced receptor that transduces the cytotoxic signal from TRAIL. Curr Biol 7: 693–696

    PubMed  CAS  Google Scholar 

  • Shaham S, Horvitz HR (1996) An alternatively spliced C. elegans ced-4 RNA encodes a novel cell death inhibitor. Cell 86: 201–208

    PubMed  CAS  Google Scholar 

  • Shav-Tal Y, Cohen M, Lapter S, Dye B, Patton JG, Vandekerckhove J, Zipori D (2001) Nuclear relocalization of the pre-mRNA splicing factor PSF during apoptosis involves hyperphosphorylation, masking of antigenic epitopes, and changes in protein interactions. Mol Biol Cell 12 (8): 2328–2340

    PubMed  CAS  Google Scholar 

  • Shaw G, Kamen R (1986) A conserved AU sequence from the 3’ untranslated region of GM-CSF mRNA mediates selection mRNA degradation. Cell 46: 659–667

    PubMed  CAS  Google Scholar 

  • Shiraiwa N, Inohara N, Okaka S, Yuzaki M, Shoji S, Ohta S (1996) An additional form of rat Bd-x, Bcl-xbeta, generated by an unspliced RNA, promotes apoptosis in promyeloid cells. J Biol Chem 271: 13258

    Google Scholar 

  • Siegmund D, Mauri D, Peters N, Juo P, Thome M, Reichwein M, Blenis J, Scheurich P, Tschopp J, Wajant H (2001) Fas-associated death domain protein (FADD) and caspase-8 mediate up-regulation of c-Fos by Fas ligand and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) via a FLICE inhibitory protein (FLIP)-regulated pathway. J Biol Chem 276 (35): 32585–32590

    PubMed  CAS  Google Scholar 

  • Sirand-Pugnet P, Durosay P, Brody E, Marie J (1995) An intronic ( A/U)GGG repeat enhances the splicing of an alternative intron of the chicken beta-tropomyosin pre-mRNA. Nucleic Acids Res 23: 3501–3507

    Google Scholar 

  • Smith CW, Valcarcel J (2000) Alternative pre-mRNA splicing: the logic of combinatorial control. Trends Biochem Sci 25 (8): 381–388

    PubMed  CAS  Google Scholar 

  • Smith CW, Patton JG, Nadal-Ginard B (1989) Alternative splicing in the control of gene expression. Annu Rev Genet 23: 527–577

    PubMed  CAS  Google Scholar 

  • Spector MS, Desnoyers S, Hoeppner DJ, Hengartner MO (1997) Interaction between the C. elegans cell-death regulators CED-9 and CED-4. Nature 385: 653–656

    PubMed  CAS  Google Scholar 

  • Srinivasula SM, Ahmad M, Guo Y, Zhan Y, Lazebnik Y, Fernandes-Alnemri T (1999) Identification of an endogenous dominant-negative short isoform of caspase-9 that can regulate apoptosis. Cancer Res 59 (5): 999–1002

    PubMed  CAS  Google Scholar 

  • Staley JP, Guthrie C (1998) Mechanical devices of the spliceosome: motors, clocks, springs, and things. Cell 92 (3): 315–326

    PubMed  CAS  Google Scholar 

  • Sterner DA, Carlo T, Berget SM (1996) Architectural limits on split genes. Proc Natl Acad Sci USA 93: 15081–15085

    PubMed  CAS  Google Scholar 

  • Sun YF, Yu LY, Saarma M, Timmusk T, Arumae U (2001) Neuron-specific Bd-2 homology 3 domain-only splice variant of Bak is anti-apoptotic in neurons, but pro-apoptotic in non-neuronal cells. J Biol Chem 276 (l9): 16240–16247

    PubMed  CAS  Google Scholar 

  • Tacke R, Manley JL (1999) Determinants of SR protein specificity. Curr Opin Cell Biol 11:358–362 Talapatra S, Thompson CB (2001) Growth factor signaling in cell survival: implications for cancer treatment. J Pharmacol Exp Ther 298 (3): 873–878

    Google Scholar 

  • Tanaka S, Saito K, Reed JC (1993) Structure-function analysis of the Bd-2 oncoprotein, addition of a heterologous transmembrane domain portions of the Bcl-2b protein restores function as a regulator of cell survival. J Biol Chem 268: 10920–10926

    PubMed  CAS  Google Scholar 

  • Thiede B, Dimmler C, Siejak F, Rudel T (2001) Predominant identification of RNA-binding proteins in Fas-induced apoptosis by proteome analysis. J Biol Chem 276: 26044–26050

    PubMed  CAS  Google Scholar 

  • Thompson CB (1995) Apoptosis in the pathogenesis and treatment of disease. Science 267: 1456–1462

    PubMed  CAS  Google Scholar 

  • Tian Q, Streuli M, Saito H, Schlossman SF, Anderson P (1991) A polyadenylate binding protein localized to the granules of cytolytic lymphocytes induces DNA fragmentation in target cells. Cell 67 (3): 629–639

    PubMed  CAS  Google Scholar 

  • Tsujimoto Y, Croce C (1986) Analysis of the structure, transcripts, and protein products of bd-2, the gene involved in human follicular lymphoma. Proc Natl Acad Sci USA 83: 5214–5218

    PubMed  CAS  Google Scholar 

  • Utz PJ, Hottelet M, Venrooij WJV, Anderson P (1998) Association of phosphorylated serine/ arginine ( SR) splicing factors with the Ul-small ribonucleoprotein (snRNP) autoantigen complex accompanies apoptotic cell death. J Exp Med 187: 547–560

    Google Scholar 

  • Valcarcel J, Green MR. (1996) The SR protein family: pleiotropic functions in pre-mRNA splicing. Trends Biochem Sci 21 (8): 296–301

    PubMed  CAS  Google Scholar 

  • Walke DW, Morgan JI (2000) A comparison of the expression and properties of Apaf-1 and Apaf-1L. Brain Res 886 (1–2): 73–81

    PubMed  CAS  Google Scholar 

  • Wang J, Manley JL (1997) Regulation of pre-mRNA splicing in Metazoa. Curr Opin Genet Dev 7 (2): 205–211

    PubMed  CAS  Google Scholar 

  • Wang L, Miura M, Bergeron L, Zhu H, Yuan J (1994) Ich-1, an Ice/ced-3-related gene, encodes both positive and negative regulators of programmed cell death. Cell 78: 739–750

    PubMed  CAS  Google Scholar 

  • Wang S, Miura M, Jung YK, Zhu H, Li E, Yuan T (1998) Murine caspase-I1, an ICE-interacting protease, is essential for the activation of ICE. Cell 92: 501–509

    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

    PubMed  CAS  Google Scholar 

  • Wei N, Lin CQ, Modafferi EF, Gomes WA, Black DL (1997) A unique intronic splicing enhancer controls the inclusion of the agrin Y exon. RNA 3: 1275–88

    PubMed  CAS  Google Scholar 

  • Whitman S, Wang X, Shalaby R, Shtivelman E (2000) Alternatively spliced products CC3 and TC3 have opposing effects on apoptosis. Mol Cell Biol 20 (2): 583–593

    PubMed  CAS  Google Scholar 

  • Wu D, Wallen HD, Nunez G (1997) Interaction and regulation of sub cellular localization of CED-4 by CED-9. Science 275: 1126–1129

    PubMed  CAS  Google Scholar 

  • Wu W, Wallen HD, Inohara N, Nunez G (1997) Interaction and regulation of the Caenorhabditis elegans death protease CED-3 by CED-4 and CED-9. J Biol Chem 272: 21449–21454

    PubMed  CAS  Google Scholar 

  • Xu R, Teng J, Cooper TA (1993) A unique intronic splicing enhancer controls the inclusion of the agrin Y exon. Mol Cell Biol 13: 3660–3674

    PubMed  CAS  Google Scholar 

  • Yang XF, Weber GF, Cantor H (1997) A novel Bd-x isoform connected to the T cell receptor regulates apoptosis in T cells. Immunity 7: 629–639

    PubMed  CAS  Google Scholar 

  • Youn BS, Zhang SM, Broxmeyer HE, Cooper S, Antol K, Fraser M Jr, Kwon BS (1998) Characterization of CKbeta8 and CKbeta8–1: two alternatively spliced forms of human beta-chemokine, chemoattractants for neutrophils, monocytes, and lymphocytes, and potent agonists at CC chemokine receptor 1. Blood 91 (9): 3118–3126

    PubMed  CAS  Google Scholar 

  • Yuan J, Shaham S, Ledoux S, Ellis HM, Horvitz HR (1993) The C. elegans cell death gene ced-3 encodes a protein similar to mammalian interleukin-1 beta-converting enzyme. Cell 75: 641–652

    PubMed  CAS  Google Scholar 

  • Zhang L, Ashiya M, Sherman TG, Grabowski PJ (1996) Essential nucleotides direct neuron-specific splicing of gamma 2 pre-mRNA. RNA 2: 682–698

    PubMed  CAS  Google Scholar 

  • Zhao Q, Schoborg RV, Pintel DJ (1994) Alternative splicing of pre-mRNAs encoding the nonstructural proteins of minute virus of mice is facilitated by sequences within the downstream exon. J Virol 68: 2849–2859

    PubMed  CAS  Google Scholar 

  • Zou H, Henzel WJ, Liu XS, Lutschg A, Wang XD (1997) Apaf-1, a human protein homologous to C. elegans CED-4, participates in cytochrome c-dependent activation of caspase-3. Cell 90: 405–413

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pediatrics and Department of Molecular Biology and Pharmacology, MPRB Rm3107, Washington University School of Medicine, St. Louis, Missouri, 63110, USA

    N. Havlioglu

Authors
  1. J. Y. Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. H. Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. N. Havlioglu
    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

Wu, J.Y., Tang, H., Havlioglu, N. (2003). Alternative Pre-mRNA Splicing and Regulation of Programmed Cell Death. 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_6

Download citation

  • DOI: https://doi.org/10.1007/978-3-662-09728-1_6

  • 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