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Multiple Roles of the SR Protein Family in Splicing Regulation

  • Chapter
Regulation of Alternative Splicing

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

Abstract

The serine and arginine-rich proteins (SR proteins) are a highly conserved family of essential pre-mRNA splicing factors. SR proteins have a modular domain structure consisting of RNA binding and protein-protein interaction modules. SR proteins function as molecular adapters, mediating interactions between the pre-mRNA and the assembling spliceosome. Unlike most essential splicing factors, SR proteins have acquired an inherent flexibility that allows them to function at numerous steps in spliceosome assembly and therefore, to play key roles in regulation of splice site selection. In the postgenomics era it is widely accepted that alternative splicing of pre-mRNAs may significantly expand the capacity of the genome to generate the functional complexity of the proteome. Therefore, it is essential to understand both the mechanisms of splice site selection and how trans-acting factors, such as the SR proteins, are regulated. Within this chapter we will discuss how the structure of SR proteins influences their roles in alternative splice site selection.

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References

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

    PubMed  CAS  Google Scholar 

  • Abovich N, Liao XC, Rosbash M (1994) The yeast MUD2 protein: an interaction with PRP11 defines a bridge between commitment complexes and U2 snRNP addition. Genes Dev 8: 843–854

    PubMed  CAS  Google Scholar 

  • Ayane M, Preuss U, Kohler G, Nielsen PJ (1991) A differentially expressed murine RNA encoding a protein with similarities to two types of nucleic acid binding motifs. Nucleic Acids Res 19: 1273–1278

    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

    PubMed  CAS  Google Scholar 

  • Bentley D (1999) Coupling RNA polymerase II transcription with pre-mRNA processing. Curr Opin Cell Biol 11: 347–351

    PubMed  CAS  Google Scholar 

  • Berget SM (1995) Exon recognition in vertebrate splicing. J Biol Chem 270: 2411–2414

    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

    PubMed  CAS  Google Scholar 

  • Birney E, Kumar S, Krainer AR (1993) Analysis of the RNA-recognition motif and RS and RGG domains: conservation in metazoan pre-mRNA splicing factors. Nucleic Acids Res 21: 5803–5816

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Black DL, Chabot B, Steitz JA (1985) U2 as well as Ul small nuclear ribonucleoproteins are involved in premessenger RNA splicing. Cell 42: 737–750

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Blencowe BJ, Bowman JA, McCracken S, Rosonina E (1999) SR-related proteins and the processing of messenger RNA precursors. Biochem Cell Biol 77: 277–291

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Bruzik JP, Maniatis T (1995) Enhancer-dependent interaction between 5’ and 3’ splice sites in trans. Proc Natl Acad Sci USA 92: 7056–7059

    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

    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

    PubMed  CAS  Google Scholar 

  • Caceres JF, Screaton GR, Krainer AR (1998) A specific subset of SR proteins shuttles continuously between the nucleus and the cytoplasm. Genes Dev 12: 55–66

    PubMed  CAS  Google Scholar 

  • Cavaloc Y, Bourgeois CF, Kister L, Stevenin J (1999) The splicing factors 9G8 and SRp20 trans-activate splicing through different and specific enhancers. RNA 5: 468–483

    PubMed  CAS  Google Scholar 

  • Champlin DT, Frasch M, Saumweber H, Lis JT (1991) Characterization of a Drosophila protein associated with boundaries of transcriptionally active chromatin. Genes Dev 5: 1611–1621

    PubMed  CAS  Google Scholar 

  • Chandler SD, Mayeda A, Yeakley JM, Krainer AR, Fu XD (1997) RNA splicing specificity determined by the coordinated action of RNA recognition motifs in SR proteins. Proc Natl Acad Sci USA 94: 3596–3601

    PubMed  CAS  Google Scholar 

  • Chiara MD, Reed R (1995) A two-step mechanism for 5’ and 3’ splice-site pairing. Nature 375: 510–513

    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 

  • Cramer P, Pesce CG, Baralle FE, Kornblihtt AR (1997) Functional association between promoter structure and transcript alternative splicing. Proc Natl Acad Sci USA 94: 11456–11460

    PubMed  CAS  Google Scholar 

  • Cramer P, Caceres JF, Cazalla D, Kadener S, Muro AF, Baralle FE, Kornblihtt AR (1999) Coupling of transcription with alternative splicing: RNA pol II promoters modulate SF2/ASF and 9G8 effects on an exonic splicing enhancer. Mol Cell 4: 251–258

    PubMed  CAS  Google Scholar 

  • Dauksaite V, Akusjarvi G (2002) Human splicing factor ASF/SF2 encodes for a repressor domain required for its inhibitory activity on pre-mRNA splicing. J Biol Chem 277: 12579–12586

    PubMed  CAS  Google Scholar 

  • Dauwalder B, Mattox W (1998) Analysis of the functional specificity of RS domains in vivo. EMBO J 17: 6049–6060

    PubMed  CAS  Google Scholar 

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

    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

    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 

  • Fu XD (1993) Specific commitment of different pre-mRNAs to splicing by single SR proteins. Nature 365: 82–85

    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 (1990) Factor required for mammalian spliceosome assembly is localized to discrete regions in the nucleus. Nature 343: 437–441

    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

    PubMed  CAS  Google Scholar 

  • Gallego ME, Gattoni R, Stevenin J, Marie J, Expert-Bezancon A (1997) The SR splicing factors ASF/SF2 and SC35 have antagonistic effects on intronic enhancer-dependent splicing of the beta-tropomyosin alternative exon 6A. EMBO J 16: 1772–1784

    PubMed  CAS  Google Scholar 

  • Ge H, Manley JL (1990) A protein factor, ASF, controls cell-specific alternative splicing of SV40 early pre-mRNA in vitro. Cell 62: 25–34

    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

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Graveley BR, Maniatis T (1998) Arginine/serine-rich domains of SR proteins can function as activators of pre-mRNA splicing. Mol Cell 1: 765–771

    PubMed  CAS  Google Scholar 

  • Graveley BR, Hertel KJ, Maniatis T (1998) A systematic analysis of the factors that determine the strength of pre-mRNA splicing enhancers. EMBO J 17: 6747–6756

    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

    PubMed  CAS  Google Scholar 

  • Hanamura A, Caceres JF, Mayeda A, Franza BR, Krainer AR (1998) Regulated tissue-specific expression of antagonistic pre-mRNA splicing factors. RNA 4: 430–444

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Hedley ML, Amrein H, Maniatis T (1995) An amino acid sequence motif sufficient for subnuclear localization of an arginine/serine-rich splicing factor. Proc Natl Acad Sci USA 92: 1152411528

    Google Scholar 

  • Hertel KJ, Maniatis T (1999) Serine-arginine ( SR)-rich splicing factors have an exon-independent function in pre-mRNA splicing. Proc Natl Acad Sci USA 96: 2651–2655

    Google Scholar 

  • Hirose Y, Manley JL (2000) RNA polymerase II and the integration of nuclear events. Genes Dev 14: 1415–1429

    PubMed  CAS  Google Scholar 

  • Hoffman BE, Lis JT (2000) Pre-mRNA splicing by the essential Drosophila protein B52: tissue and target specificity. Mol Cell Biol 20: 181–186

    PubMed  CAS  Google Scholar 

  • Hoffman DW, Query CC, Golden BL, White SW, Keene JD (1991) RNA-binding domain of the A protein component of the U1 small nuclear ribonucleoprotein analyzed by NMR spectroscopy is structurally similar to ribosomal proteins. Proc Natl Acad Sci USA 88: 2495–2499

    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

    PubMed  CAS  Google Scholar 

  • Jensen KB, Dredge BK, Stefani G, Zhong R, Buckanovich RJ, Okano HJ, Yang YY, Darnell RB (2000) Nova-1 regulates neuron-specific alternative splicing and is essential for neuronal viability. Neuron 25: 359–371

    PubMed  CAS  Google Scholar 

  • Jumaa H, Nielsen PJ (1997) The splicing factor SRp20 modifies splicing of its own mRNA and ASF/SF2 antagonizes this regulation. EMBO J 16: 5077–5085

    PubMed  CAS  Google Scholar 

  • Jumaa H, Wei G, Nielsen PJ (1999) Blastocyst formation is blocked in mouse embryos lacking the splicing factor SRp20. Curr Biol 9: 899–902

    PubMed  CAS  Google Scholar 

  • Kadener S, Cramer P, Nogues G, Cazalla D, de la Mata M, Fededa JP, Werbajh SE, Srebrow A, Kornblihtt AR (2001) Antagonistic effects of T-Ag and VP16 reveal a role for RNA pol II elongation on alternative splicing. EMBO J 20: 5759–5768

    PubMed  CAS  Google Scholar 

  • Kan JL, Green MR (1999) Pre-mRNA splicing of IgM exons M1 and M2 is directed by a juxtaposed splicing enhancer and inhibitor. Genes Dev 13: 462–471

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Kawano T, Fujita M, Sakamoto H (2000) Unique and redundant functions of SR proteins, a conserved family of splicing factors, in Caenorhabditis elegans development. Mech Dev 95: 67–76

    Google Scholar 

  • Kenan DJ, Query CC, Keene JD (1991) RNA recognition: towards identifying determinants of specificity. Trends Biochem Sci 16: 214–220

    PubMed  CAS  Google Scholar 

  • Kim YJ, Baker BS (1993) Isolation of RRM-type RNA-binding protein genes and the analysis of their relatedness by using a numerical approach. Mol Cell Biol 13: 174–183

    PubMed  CAS  Google Scholar 

  • Kim YJ, Zuo P, Manley JL, Baker BS (1992) The Drosophila RNA-binding protein RBP1 is localized to transcriptionally active sites of chromosomes and shows a functional similarity to human splicing factor ASF/SF2.Genes Dev 6: 2569–2579

    CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Krainer AR, Maniatis T (1985) Multiple factors including the small nuclear ribonucleoproteins Ul and U2 are necessary for pre-mRNA splicing in vitro. Cell 42: 725–736

    PubMed  CAS  Google Scholar 

  • Krainer AR, Conway GC, Kozak D (1990a) Purification and characterization of pre-mRNA splicing factor SF2 from HeLa cells. Genes Dev 4: 1158–1171

    PubMed  CAS  Google Scholar 

  • Krainer AR, Conway GC, Kozak D (1990b) The essential pre-mRNA splicing factor SF2 influences 5’ splice site selection by activating proximal sites. Cell 62: 35–42

    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

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

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

    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

    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

    PubMed  CAS  Google Scholar 

  • Lazar G, Schaal T, Maniatis T, Goodman HM (1995) Identification of a plant serine-arginine-rich protein similar to the mammalian splicing factor SF2/ASF. Proc Natl Acad Sci USA 92: 7672–7676

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Li H, Bingham PM Arginine/serine-rich domains of the su(wa) and tra RNA processing regulators target proteins to a subnuclear compartment implicated in splicing. (1991) Cell 67: 335–342

    PubMed  CAS  Google Scholar 

  • Li X, Shambaugh ME, Rottman FM, Bokar JA (2000) SR proteins Asf/SF2 and 9G8 interact to activate enhancer-dependent intron D splicing of bovine growth hormone pre-mRNA in vitro. RNA 6: 1847–1858

    PubMed  CAS  Google Scholar 

  • Lim LP, Burge CB (2001) A computational analysis of sequence features involved in recognition of short introns. Proc Natl Acad Sci USA 98: 11193–11198

    PubMed  CAS  Google Scholar 

  • Liu HX, Zhang M, Krainer AR (1998) Identification of functional exonic splicing enhancer motifs recognized by individual SR proteins. Genes Dev 12: 1998–2012

    PubMed  CAS  Google Scholar 

  • Liu HX, Chew SL, Cartegni L, Zhang MQ, Krainer AR (2000) Exonic splicing enhancer motif recognized by human SC35 under splicing conditions. Mol Cell Biol 20: 1063–1071

    PubMed  CAS  Google Scholar 

  • Longman D, Johnstone IL, Caceres JF (2000) Functional characterization of SR and SR-related genes in Caenorhabditis elegans. EMBO J 19: 1625–1637

    PubMed  CAS  Google Scholar 

  • Longman D, McGarvey T, McCracken S, Johnstone IL, Blencowe BJ, Caceres JF (2001) Multiple interactions between SRm160 and SR family proteins in enhancer-dependent splicing and development of C. elegans. Curr Biol 11: 1923–1933

    PubMed  CAS  Google Scholar 

  • Lopato S, Mayeda A, Krainer AR, Barta A (1996a) Pre-mRNA splicing in plants: characterization of Ser/Arg splicing factors. Proc Natl Acad Sci USA 93: 3074–3079

    PubMed  CAS  Google Scholar 

  • Lopato S, Waigmann E, Barta A (1996b) Characterization of a novel arginine/serine-rich splicing factor in Arabidopsis. Plant Cell 8: 2255–2264

    PubMed  CAS  Google Scholar 

  • Lopato S, Kalyna M, Dorner S, Kobayashi R, Krainer AR, Barta A (1999) atSRp30, one of two SF2/ASF-like proteins from Arabidopsis thaliana, regulates splicing of specific plant genes. Genes Dev 13: 987–1001

    Google Scholar 

  • Lutz CS, Alwine JC (1994) Direct interaction of the U1 snRNP-A protein with the upstream efficiency element of the SV40 late polyadenylation signal. Genes Dev 8: 576–586

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Matter N, Marx M, Weg-Remers S, Ponta H, Herrlich P, Konig H (2000) Heterogeneous ribonucleoprotein Al is part of an exon-specific splice-silencing complex controlled by oncogenic signaling pathways. J Biol Chem 275: 35353–35360

    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

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Mayeda A, Screaton GR, Chandler SD, Fu XD, Krainer AR (1999) Substrate specificities of SR proteins in constitutive splicing are determined by their RNA recognition motifs and composite pre-mRNA exonic elements. Mol Cell Biol 19: 1853–1863

    PubMed  CAS  Google Scholar 

  • Misteli T (2000) Cell biology of transcription and pre-mRNA splicing: nuclear architecture meets nuclear function. J Cell Sci 113 (Pt 11): 1841–1849

    PubMed  CAS  Google Scholar 

  • Nagai K, Oubridge C, Jessen TH, Li J, Evans PR (1990) Crystal structure of the RNA-binding domain of the Ul small nuclear ribonucleoprotein A. Nature 348: 515–520

    PubMed  CAS  Google Scholar 

  • Nagai K, Oubridge C, Ito N, Jessen TH, Avis J, Evans P (1995) Crystal structure of the U1 A spliceosomal protein complexed with its cognate RNA hairpin. Nucleic Acids Symp Ser 1–2

    Google Scholar 

  • Neubauer G, King A, Rappsilber J, Calvio C, Watson M, Ajuh P, Sleeman J, Lamond A, Mann M (1998) Mass spectrometry and EST-database searching allows characterization of the multi-protein spliceosome complex. Nat Genet 20: 46–50

    PubMed  CAS  Google Scholar 

  • Nilsen TW (2000) The case for an RNA enzyme. Nature 408: 782–783

    PubMed  CAS  Google Scholar 

  • Nilsen TW (2002) The spliceosome: no assembly required? Mol Cell 9: 8–9

    PubMed  CAS  Google Scholar 

  • Parker R, Siliciano PG, Guthrie C (1987) Recognition of the TACTAAC box during mRNA splicing in yeast involves base pairing to the U2-like snRNA. Cell 49: 229–239

    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

    PubMed  CAS  Google Scholar 

  • Peng X, Mount SM (1995) Genetic enhancement of RNA-processing defects by a dominant mutation in B52, the Drosophila gene for an SR protein splicing factor. Mol Cell Biol 15: 6273–6282

    PubMed  CAS  Google Scholar 

  • Polydorides AD, Okano HJ, Yang YY, Stefani G, Darnell RB (2000) A brain-enriched polypyrimidine tract-binding protein antagonizes the ability of Nova to regulate neuron-specific alternative splicing. Proc Natl Acad Sci USA 97: 6350–6355

    PubMed  CAS  Google Scholar 

  • Query CC, Moore MJ, Sharp PA (1994) Branch nucleophile selection in pre-mRNA splicing: evidence for the bulged duplex model. Genes Dev 8: 587–597

    PubMed  CAS  Google Scholar 

  • Reed R (2000) Mechanisms of fidelity in pre-mRNA splicing. Curr Opin Cell Biol 12: 340–345

    PubMed  CAS  Google Scholar 

  • Ring HZ, Lis JT (1994) The SR protein B52/SRp55 is essential for Drosophila development. Mol Cell Biol 14: 7499–7506

    PubMed  CAS  Google Scholar 

  • Romfo CM, Alvarez CJ, van Heeckeren WJ, Webb CJ, Wise JA (2000) Evidence for splice site pairing via intron definition in Schizosaccharomyces pombe. Mol Cell Biol 20: 7955–7970

    PubMed  CAS  Google Scholar 

  • Romfo CM, Maroney PA, Wu S, Nilsen TW (2001) 3’ splice site recognition in nematode transsplicing involves enhancer-dependent recruitment of U2 snRNP. RNA 7: 785–792

    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 

  • 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

    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

    PubMed  CAS  Google Scholar 

  • Sanford JR, Bruzik JP (1999) SR proteins are required for nematode trans-splicing in vitro. RNA 5: 918–928

    PubMed  CAS  Google Scholar 

  • Schaal TD, Maniatis T (1999) Selection and characterization of pre-mRNA splicing enhancers: identification of novel SR protein-specific enhancer sequences. Mol Cell Biol 19: 1705–1719

    PubMed  CAS  Google Scholar 

  • Scherly D, Boelens W, van Venrooij WJ, Dathan NA, Hamm J, Mattaj IW (1989) Identification of the RNA binding segment of human Ul A protein and definition of its binding site on Ul snRNA. EMBO J 8: 4163–4170

    PubMed  CAS  Google Scholar 

  • Screaton GR, Caceres 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

    PubMed  CAS  Google Scholar 

  • Staknis D, Reed R (1994) SR proteins promote the first specific recognition of Pre-mRNA and are present together with the Ul small nuclear ribonucleoprotein particle in a general splicing enhancer complex. Mol Cell Biol 14: 7670–7682

    PubMed  CAS  Google Scholar 

  • Stevens SW, Ryan DE, Ge HY, Moore RE, Young MK, Lee TD, Abelson J (2002) Composition and functional characterization of the yeast spliceosomal penta-snRNP. Mol Cell 9: 31–44

    PubMed  CAS  Google Scholar 

  • Surowy CS, van Santen VL, Scheib-Wixted SM, Spritz RA (1989) Direct, sequence-specific binding of the human U1–70K ribonucleoprotein antigen protein to loop I of Ul small nuclear RNA. Mol Cell Biol 9: 4179–4186

    PubMed  CAS  Google Scholar 

  • Tacke R, Manley JL (1995) The human splicing factors ASF/SF2 and SC35 possess distinct, functionally significant RNA binding specificities. EMBO J 14: 3540–3551

    PubMed  CAS  Google Scholar 

  • Tacke R, Manley JL (1999) Determinants of SR protein specificity. Curr Opin Cell Biol 11: 358362

    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

    PubMed  CAS  Google Scholar 

  • Talerico M, Berget SM (1994) Intron definition in splicing of small Drosophila introns. Mol Cell Biol 14: 3434–3445

    PubMed  CAS  Google Scholar 

  • Teigelkamp S, Mundt C, Achsel T, Will CL, Luhrmann R (1997) The human U5 snRNP-specific 100-kD protein is an RS domain-containing, putative RNA helicase with significant homology to the yeast splicing factor Prp28p.RNA 3: 1313–1326

    CAS  Google Scholar 

  • Tuerk C, Gold L (1990) Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase. Science 249: 505–510

    PubMed  CAS  Google Scholar 

  • Valcarcel J, Gaur RK, Singh R, Green MR (1996) Interaction of U2AF65 RS region with pre-mRNA branch point and promotion of base pairing with U2 snRNA. Science 273: 1706–1709

    PubMed  CAS  Google Scholar 

  • van Der Houven Van Oordt W, Newton K, Screaton GR, Caceres JF (2000A) Role of SR protein modular domains in alternative splicing specificity in vivo. Nucleic Acids Res 28: 4822–4831

    Google Scholar 

  • van Der Houven Van Oordt W, Diaz-Meco MT, Lozano J, Krainer AR, Moscat J, Caceres JF (2000b) 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

    Google Scholar 

  • Vellard M, Sureau A, Soret J, Martinerie C, Perbal B (1992) A potential splicing factor is encoded by the opposite strand of the trans-spliced c-myb exon. Proc Natl Acad Sci USA 89: 25112515

    Google Scholar 

  • Wang HY, Xu X, Ding JH, Bermingham JR Jr, Fu XD (2001) SC35 plays a role in T cell development and alternative splicing of CD45. Mol Cell 7: 331–342

    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 J, Xiao SH, Manley JL (1998) Genetic analysis of the SR protein ASF/SF2: interchangeability of RS domains and negative control of splicing. Genes Dev 12: 2222–2233

    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

    PubMed  CAS  Google Scholar 

  • Will CL, Luhrmann R (2001) Spliceosomal UsnRNP biogenesis, structure and function. Curr Opin Cell Biol 13: 290–301

    PubMed  CAS  Google Scholar 

  • Wittekind M, Gorlach M, Friedrichs M, Dreyfuss G, Mueller L (1992) 1H, 13C, and 15N NMR assignments and global folding pattern of the RNA-binding domain of the human hnRNP C proteins. Biochemistry 31: 6254–6265

    Google Scholar 

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

    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

    PubMed  CAS  Google Scholar 

  • Xiao SH, Manley JL (1997) Phosphorylation of the ASF/SF2 RS domain affects both protein-protein and protein-RNA interactions and is necessary for splicing. Genes Dev 11: 334344

    Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Yang X, Bani MR, Lu SJ, Rowan S, Ben David Y, Chabot B (1994) The Al and A1B proteins of heterogeneous nuclear ribonucleoparticles modulate 5’ splice site selection in vivo. Proc Natl Acad Sci USA 91: 6924–6928

    PubMed  CAS  Google Scholar 

  • Zahler AM (1999) Purification of SR protein splicing factors. Methods Mol Biol 118: 419–432

    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

    PubMed  CAS  Google Scholar 

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

    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: 92439247

    Google Scholar 

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

    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

    PubMed  CAS  Google Scholar 

  • Zhuang Y, Weiner AM (1986) A compensatory base change in U1 snRNA suppresses a 5’ splice site mutation. Cell 46: 827–835

    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

    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 

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Sanford, J.R., Longman, D., Cáceres, J.F. (2003). Multiple Roles of the SR Protein Family in Splicing Regulation. 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_2

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