Cell signalling and the control of pre-mRNA splicing - Nature Reviews Molecular Cell Biology
- ️Manley, James L.
- ️Wed Sep 01 2004
Mironov, A. A., Fickett, J. W. & Gelfand, M. S. Frequent alternative splicing of human genes. Genome Res. 9, 1288–1293 (1999).
Johnson, J. M. et al. Genome-wide survey of human alternative pre-mRNA splicing with exon junction microarrays. Science 302, 2141–2144 (2003).
Kan, Z., Rouchka, E. C., Gish, W. R. & States, D. J. Gene structure prediction and alternative splicing analysis using genomically aligned ESTs. Genome Res. 11, 889–900 (2001).
Modrek, B., Resch, A., Grasso, C. & Lee, C. Genome-wide analysis of alternative splicing using human expressed sequence data. Nucleic Acids Res. 29, 2850–2859 (2001).
Blencowe, B. J. Exonic splicing enhancers: mechanism of action, diversity and role in human genetic diseases. Trends Biochem. Sci. 25, 106–110 (2000).
Smith, C. W. & Valcarcel, J. Alternative pre-mRNA splicing: the logic of combinatorial control. Trends Biochem. Sci. 25, 381–388 (2000).
Grabowski, P. J. & Black, D. L. Alternative RNA splicing in the nervous system. Prog. Neurobiol. 65, 289–308 (2001).
Graveley, B. R. Alternative splicing: increasing diversity in the proteomic world. Trends Genet. 17, 100–107 (2001).
Maniatis, T. & Tasic, B. Alternative pre-mRNA splicing and proteome expansion in metazoans. Nature 418, 236–243 (2002).
Black, D. L. Mechanisms of alternative pre-messenger RNA splicing. Annu. Rev. Biochem. 72, 291–336 (2003).
Manley, J. L. & Tacke, R. SR proteins and splicing control. Genes Dev. 10, 1569–1579 (1996).
Graveley, B. R. Sorting out the complexity of SR protein functions. RNA 6, 1197–1211 (2000).
Wu, J. Y. & Maniatis, T. Specific interactions between proteins implicated in splice site selection and regulated alternative splicing. Cell 75, 1061–1070 (1993).
Kohtz, J. D. et al. Protein–protein interactions and 5′-splice-site recognition in mammalian mRNA precursors. Nature 368, 119–124 (1994).
Xiao, S. H. & Manley, J. L. Phosphorylation of the ASF/SF2 RS domain affects both protein–protein and protein–RNA interactions and is necessary for splicing. Genes Dev. 11, 334–344 (1997).
Xiao, S. H. & Manley, J. L. Phosphorylation–dephosphorylation differentially affects activities of splicing factor ASF/SF2. EMBO J. 17, 6359–6367 (1998).
Gui, J. F., Lane, W. S. & Fu, X. D. A serine kinase regulates intracellular localization of splicing factors in the cell cycle. Nature 369, 678–682 (1994).
Colwill, K. et al. The Clk/Sty protein kinase phosphorylates SR splicing factors and regulates their intranuclear distribution. EMBO J. 15, 265–275 (1996).
Duncan, P. I. et al. Alternative splicing of STY, a nuclear dual specificity kinase. J. Biol. Chem. 270, 21524–21531 (1995).
Lee, K., Du, C., Horn, M. & Rabinow, L. Activity and autophosphorylation of LAMMER protein kinases. J. Biol. Chem. 271, 27299–27303 (1996).
Nayler, O., Stamm, S. & Ullrich, A. Characterization and comparison of four serine- and arginine-rich (SR) protein kinases. Biochem. J. 326, 693–700 (1997).
Prasad, J., Colwill, K., Pawson, T. & Manley, J. L. The protein kinase Clk/Sty directly modulates SR protein activity: both hyper- and hypophosphorylation inhibit splicing. Mol. Cell. Biol. 19, 6991–7000 (1999).
Prasad, J. & Manley, J. L. Regulation and substrate specificity of the SR protein kinase Clk/Sty. Mol. Cell. Biol. 23, 4139–4149 (2003).
Ko, T. K., Kelly, E. & Pines, J. CrkRS: a novel conserved Cdc2-related protein kinase that colocalises with SC35 speckles. J. Cell Sci. 114, 2591–2603 (2001).
Hirose, Y. & Manley, J. L. RNA polymerase II and the integration of nuclear events. Genes Dev. 14, 1415–1429 (2000).
Proudfoot, N. J., Furger, A. & Dye, M. J. Integrating mRNA processing with transcription. Cell 108, 501–512 (2002).
Maniatis, T. & Reed, R. An extensive network of coupling among gene expression machines. Nature 416, 499–506 (2002).
Dreyfuss, G., Matunis, M. J., Pinol-Roma, S. & Burd, C. G. hnRNP proteins and the biogenesis of mRNA. Annu. Rev. Biochem. 62, 289–321 (1993).
Mayeda, A. & Krainer, A. R. Regulation of alternative pre-mRNA splicing by hnRNP A1 and splicing factor SF2. Cell 68, 365–375 (1992).
Singh, R., Valcarcel, J. & Green, M. R. Distinct binding specificities and functions of higher eukaryotic polypyrimidine tract-binding proteins. Science 268, 1173–1176 (1995).
Ruskin, B., Zamore, P. D. & Green, M. R. A factor, U2AF, is required for U2 snRNP binding and splicing complex assembly. Cell 52, 207–219 (1988).
Labourier, E. et al. Antagonism between RSF1 and SR proteins for both splice-site recognition in vitro and Drosophila development. Genes Dev. 13, 740–753 (1999).
Shin, C. & Manley, J. L. The SR protein SRp38 represses splicing in M phase cells. Cell 111, 407–417 (2002). Characterizes SRp38 as a general splicing repressor that is activated by dephosphorylation, and shows that the splicing machinery is repressed by SRp38 during M phase of the cell cycle.
Kanopka, A., Muhlemann, O. & Akusjarvi, G. Inhibition by SR proteins of splicing of a regulated adenovirus pre-mRNA. Nature 381, 535–538 (1996).
Valcarcel, J., Singh, R., Zamore, P. D. & Green, M. R. The protein Sex-lethal antagonizes the splicing factor U2AF to regulate alternative splicing of transformer pre-RNA. Nature 362, 171–175 (1993).
Amrein, H., Hedley, M. L. & Maniatis, T. The role of specific protein–RNA and protein–protein interactions in positive and negative control of pre-mRNA splicing by Transformer 2. Cell 76, 735–746 (1994).
Jensen, K. B. et al. Nova-1 regulates neuron-specific alternative splicing and is essential for neuronal viability. Neuron 25, 359–371 (2000). Describes NOVA1 as a brain-specific splicing regulator by showing neuronal splicing defects in Nova1 -null mice.
Ponta, H., Sherman, L. & Herrlich, P. A. CD44: from adhesion molecules to signaling regulators. Nature Rev. Mol. Cell Biol. 4, 33–45 (2003).
Chang, L. & Karin, M. Mammalian MAP kinase signalling cascades. Nature 410, 37–40 (2001).
Konig, H., Ponta, H. & Herrlich, P. Coupling of signal transduction to alternative pre-mRNA splicing by a composite splice regulator. EMBO J. 17, 2904–2913 (1998). Provides an initial characterization of CD44 v5 alternative-splicing regulation in response to activated Ras by identifying positively and negatively acting sequences.
Weg-Remers, S., Ponta, H., Herrlich, P. & Konig, H. Regulation of alternative pre-mRNA splicing by the ERK MAP-kinase pathway. EMBO J. 20, 4194–4203 (2001).
Vernet, C. & Artzt, K. STAR, a gene family involved in signal transduction and activation of RNA. Trends Genet. 13, 479–484 (1997).
Taylor, S. J. & Shalloway, D. An RNA-binding protein associated with Src through its SH2 and SH3 domains in mitosis. Nature 368, 867–871 (1994).
Fumagalli, S., Totty, N. F., Hsuan, J. J. & Courtneidge, S. A. A target for Src in mitosis. Nature 368, 871–874 (1994).
Taylor, S. J., Resnick, R. J. & Shalloway, D. SAM68 exerts separable effects on cell cycle progression and apoptosis. BMC Cell Biol. 5, 5 (2004).
Matter, N., Herrlich, P. & Konig, H. Signal-dependent regulation of splicing via phosphorylation of SAM68. Nature 420, 691–695 (2002). Provides evidence that SAM68 activates CD44 v5 inclusion in response to phosphorylation by ERK.
Tacke, R. & Manley, J. L. The human splicing factors ASF/SF2 and SC35 possess distinct, functionally significant RNA binding specificities. EMBO J. 14, 3540–3551 (1995).
Tacke, R. Tohyama, M., Ogawa, S., & Manley, J. L. Human Tra2 proteins are sequence-specific activators of pre-mRNA splicing. Cell 93, 139–148 (1998).
Matter, N. et al. Heterogeneous ribonucleoprotein A1 is part of an exon-specific splice-silencing complex controlled by oncogenic signaling pathways. J. Biol. Chem. 275, 35353–35360 (2000).
Kashima, T. & Manley, J. L. A negative element in SMN2 exon 7 inhibits splicing in spinal muscular atrophy. Nature. Genet. 34, 460–463 (2003).
Hermiston, M. L., Xu, Z. & Weiss, A. CD45: a critical regulator of signaling thresholds in immune cells. Annu. Rev. Immunol. 21, 107–137 (2003).
Lynch, K. W. & Weiss, A. A model system for activation-induced alternative splicing of CD45 pre-mRNA in T cells implicates protein kinase C and Ras. Mol. Cell. Biol. 20, 70–80 (2000).
Lynch, K. W. & Weiss, A. A CD45 polymorphism associated with multiple sclerosis disrupts an exonic splicing silencer. J. Biol. Chem. 276, 24341–24347 (2001).
Rothrock, C., Cannon, B., Hahm, B. & Lynch. K. W. A conserved signal-responsive sequence mediates activation-induced alternative splicing of CD45. Mol. Cell 12, 1317–1324 (2003). Defines an ESS element as a signal-responsive cis -element that mediates CD45 v5 skipping.
Lemaire, R., Winne, A., Sarkissian, M. & Lafyatis, R. SF2 and SRp55 regulation of CD45 exon 4 skipping during T cell activation. Eur. J. Immunol. 29, 823–837 (1999).
ten Dam, G. B. et al. Regulation of alternative splicing of CD45 by antagonistic effects of SR protein splicing factors. J. Immunol. 164, 5287–5295 (2000).
Wu, J. Y., Tang, H. & Havlioglu, N. Alternative pre-mRNA splicing and regulation of programmed cell death. Prog. Mol. Subcell. Biol. 31, 153–185 (2003).
Chalfant, C. E. et al. FAS activation induces dephosphorylation of SR proteins; dependence on the de novo generation of ceramide and activation of protein phasphatase 1. J. Biol. Chem. 276, 44848–44855 (2001).
Bose, R. et al. Ceramide synthase mediates daunorubicin-induced apoptosis: an alternative mechanism for generating death signals. Cell 82, 405–414 (1995).
Utz, P. J., Hottelet, M., van Venrooij, W. J. & Anderson, P. Association of phosphorylated serine/Arg (SR) splicing factors with the U1-small ribonucleoprotein (snRNP) auroantigen complex accompanies apoptotic cell death. J. Exp. Med. 187, 547–560 (1998).
Chalfant, C. E. et al. De novo ceramide regulates the alternative splicing of caspase 9 and Bcl-x in A549 lung adenocarcinoma cells. Dependence on protein phosphatase-1. J. Biol. Chem. 277, 12587–12595 (2002). Provides evidence that ceramide regulates alternative splicing of transcripts that encode apoptotic regulators.
Massiello, A. et al. Identification of two RNA cis-elements that function to regulate the 5′ splice site selection of Bcl-x pre-mRNA in response to ceramide. J. Biol. Chem. 279, 15799–15804 (2004).
Forch, P. et al. The apoptosis-promoting factor TIA1 is a regulator of alternative pre-mRNA splicing. Mol. Cell 6, 1089–1098 (2000). Describes the mechanism by which TIA1 regulates alternative splicing of Fas pre-mRNA.
Forch, P., Puig, O., Martinez, C., Seraphin, B. & Valcarcel, J. The splicing regulator TIA1 interacts with U1-C to promote U1 snRNP recruitment to 5′ splice sites. EMBO J. 21, 6882–6892 (2002).
Tian, Q., Streuli, M., Schlossman, S. F. & Anderson, P. A polyadenylate binding protein localized to the granules of cytolytic lymphocytes induces DNA fragmentation in target cells. Cell 67, 629–639 (1991).
Tian, Q., Taupin, J., Elledge, S., Robertson, M. & Anderson, P. Fas-mediated serine/threonine kinase (FAST) phosphorylates TIA1 during Fas-mediated apoptosis. J. Exp. Med. 182, 865–874 (1995).
Burns, C. G. et al. Removal of a single α-tubulin gene intron suppresses cell cycle arrest phenotypes of splicing factor mutations in Saccharomyces cerevisiae. Mol. Cell. Biol. 22, 801–815 (2002).
Lopez, P. J. & Seraphin, B. Genomic-scale quantitative analysis of yeast pre-mRNA splicing: Implications for splice-site recognition. RNA 5, 1135–1137 (1999).
Segil, N., Guermah, M., Hoffmann, A., Roeder, R. G. & Heintz. N. Mitotic regulation of TFIID: inhibition of activator-dependent transcription and changes in subcellular localization. Genes Dev. 10, 2389–2400 (1996).
Akoulitchev, S. & Reinberg, D. The molecular mechanism of mitotic inhibition of TFIIH is mediated by phosphorylation of CDK7. Genes Dev. 12, 3541–3550 (1998).
Long, J. J., Leresche, A., Kriwacki, R. W. & Gottesfeld, J. M. Repression of TFIIH transcriptional activity and TFIIH associated cdk7 kinase activity at mitosis. Mol. Cell. Biol. 18, 1467–1476 (1998).
Xu, Y. X., Hirose, Y., Zhou, X. Z., Lu, K. P. & Manley, J. L. Pin1 modulates the structure and function of human RNA polymerase II. Genes Dev. 17, 2765–2776 (2003).
Colgan, D. F., Murthy, K. G., Prives, C. & Manley, J. L. Cell-cycle related regulation of poly(A) polymerase by phosphorylation. Nature 384, 282–285 (1996).
Pyronnet, S., Dostie, J. & Sonenberg, N. Suppression of cap-dependent translation in mitosis. Genes Dev. 15, 2083–2093 (2001).
Shin, C., Feng, Y. & Manley, J. L. Dephosphorylated SRp38 acts as a splicing repressor in response to heat shock. Nature 427, 553–558 (2004). Provides evidence that SRp38 is responsible for heat-shock-induced splicing repression in vitro and in vivo.
Pyronnet, S. & Sonenberg, N. Cell-cycle-dependent translational control. Curr. Opin. Genet. Dev. 11, 13–18 (2001).
Trinkle-Mulcahy, L. et al. Nuclear organization of NIPP1, a regulatory subunit of protein phosphotase 1 that associates with pre-mRNA splicing factors. J. Cell Sci. 112, 157–168 (1999).
Beullens, M. & Bollen, M. The protein phosphatase-1 regulator NIPP1 is also a splicing factor involved in a late step of spliceosome assembly. J. Biol. Chem. 277, 19855–19860 (2002).
Boudrez, A. et al. NIPP1-mediated interaction of protein phosphatase-1 with CDC5L, a regulator of pre-mRNA splicing and mitotic entry. J. Biol. Chem. 275, 25411–25417 (2000).
Boudrez, A., Beullens, M., Waelkens, E., Stalmans, W. & Bollen, M. Phosphorylation-dependent interaction between the splicing factors SAP155 and NIPP1. J. Biol. Chem. 277, 31834–31841 (2002).
Anderson, R. A., Boronenkov, I. V., Doughman, S. D., Kunz, J. & Loijens, J. C. Phosphatidylinositol phosphate kinases, a multifaceted family of signaling enzymes. J. Biol. Chem. 274, 9907–9910 (1999).
Toker, A. Phosphoinositides and signal transduction. Cell. Mol. Life Sci. 59, 761–779 (2002).
Boronenkov, I. V., Loijens, J. C., Umeda, M. & Anderson, R. A. Phosphoinositide signaling pathways in nuclei are associated with nuclear speckles containing pre-mRNA processing factors. Mol. Biol. Cell 9, 3547–3560 (1998).
Osborne, S. L., Thomas, C. L., Gschmeissner, S. & Schiavo, G. Nuclear PtdIns(4,5)P2 assembles in a mitotically regulated particle involved in pre-mRNA splicing. J. Cell Sci. 114, 2501–2511 (2001).
Yost, H. J., Petersen, R. B. & Lindquist, S. RNA metabolism: strategies for regulation in the heat shock response. Trends Genet. 6, 223–227 (1990).
Gattoni, R. et al. The human hnRNP-M proteins: structure and relation with early heat shock-induced splicing arrest and chromosome mapping. Nucleic Acids Res. 24, 2535–2542 (1996).
Mahe, D. et al. Cloning of human 2H9 heterogeneous nuclear ribonucleoproteins. Relation with splicing and early heat shock-induced splicing arrest. J. Biol. Chem. 272, 1827–1836 (1997).
Jenkins, G. M. et al. Acute activation of de novo sphingolipid biosynthesis upon heat shock causes an accumulation of ceramide and subsequent dephosphorylation of SR proteins. J. Biol. Chem. 277, 42572–42578 (2002).
Carlsson, A. A paradigm shift in brain research. Science 294, 1021–1024 (2001).
Nieoullon, A. Dopamine and the regulation of cognition and attention. Prog. Neurobiol. 67, 53–83 (2002).
Berke, J. D., Paletzki, R. F., Aronson, G. J., Hyman, S. E. & Gerfen, C. R. A complex program of striatal gene expression induced by dopaminergic stimulation. J. Neurosci. 18, 5301–5310 (1998).
Berke, J. D. et al. Dopamine and glutamate induce distinct striatal splice forms of Ania-6, an RNA polymerase II-associated cyclin. Neuron 32, 277–287 (2001).
Sgambato, V., Minassian, R., Nairn, A. C. & Hyman, S. E. Regulation of ania-6 splice variants by distinct signaling pathways in striatal neurons. J. Neurochem. 86, 153–164 (2003).
Boucher, L., Ouzounis, C. A., Enright, A. J. & Blencowe, B. J. A genome-wide survey of RS domain proteins. RNA 7, 1693–1701 (2001).
Dickinson, L. A., Edgar, A. J., Ehley, J. & Gottesfeld, J. M. Cyclin L is an RS domain protein involved in pre-mRNA splicing. J. Biol. Chem. 277, 25465–25473 (2002).
Hu, D., Mayeda, A., Trembley, J. H., Lahti, J. M. & Kidd, V. J. CDK11 complexes promote pre-mRNA splicing. J. Biol. Chem. 278, 8623–8629 (2003).
Trembley, J. H. et al. PITSLRE p110 protein kinases associate with transcription complexes and affect their activity. J. Biol. Chem. 277, 2589–2596 (2002).
Lahti, J. M., Xiang, J., Heath, L. S., Campana, D. & Kidd, V. J. PITSLRE protein kinase activity is associated with apoptosis. Mol. Cell. Biol. 15, 1–11 (1995).
Tang, D., Gururajan, R. & Kidd, V. J. Phosphorylation of PITSLRE p110 isoforms accompanies their processing by caspases during Fas-mediated cell death. J. Biol. Chem. 273, 16601–16607 (1998).
de Graaf, K. et al. Characterization of cyclin L2, a novel cyclin with an arginine/serine-rich (RS) domain: phosphorylation by DYRK1A and colocalization with splicing factors. J. Biol. Chem. 279, 4612–4624 (2004).
Yang, L. et al. Cyclin L2, a novel RNA-polymerase II-associated cyclin, is involved in pre-mRNA splicing and induces apoptosis of human hepatocellular carcinoma cells. J. Biol. Chem. 279, 11639–11648 (2004). Shows that cyclin L2 functions in splicing in vitro and that overexpression induces apoptosis.
Butler, A., Tsunoda, S., McCobb, D. P., Wei, A. & Salkoff, L. mSlo, a complex mouse gene encoding 'maxi' calcium-activated potassium channels. Science 261, 221–224 (1993).
Black, D. L. Splicing in the inner ear: a familiar tune, but what are the instruments? Neuron 20, 165–168 (1998).
Xie, J. & McCobb, D. P. Control of alternative splicing of potassium channels by stress hormones. Science 280, 443–446 (1998).
Xie, J. & Black, D. L. A CaMK IV responsive RNA element mediates depolarization-induced alternative splicing of ion channels. Nature 410, 936–939 (2001). Describes a sequence element in the STREX exon of the SLO transcript that is required for exon exclusion after depolarization-induced signalling through CaMKIV.
Yeakley, J. M. et al. Profiling alternative splicing on fiber-optic arrays. Nature Biotechnol. 20, 353–358 (2002).