Identification of Splicing Silencers and Enhancers in Sense Alus: a Role for Pseudoacceptors in Splice Site Repression

REFERENCES

• Arrisi-Mercado, P., M. Romano, A. F. Muro, and F. E. Baralle. 2004. An exonic splicing enhancer offsets the atypical GU-rich 3′ splice site of human apolipoprotein A-II exon 3. J. Biol. Chem. 279:39331–39339.
   PubMedGoogle Scholar
• Batzer, M. A., and P. L. Deininger. 2002. Alu repeats and human genomic diversity. Nat. Rev. Genet. 3:370–379.
   PubMed Web of Science ®Google Scholar
• Berget, S. M. 1995. Exon recognition in vertebrate splicing. J. Biol. Chem. 270:2411–2414.
   PubMed Web of Science ®Google Scholar
• Bilodeau, P. S., J. K. Domsic, A. Mayeda, A. R. Krainer, and C. M. Stoltzfus. 2001. RNA splicing at human immunodeficiency virus type 1 3′ splice site A2 is regulated by binding of hnRNP A/B proteins to an exonic splicing silencer element. J. Virol. 75:8487–8497.
   PubMedGoogle Scholar
• Blanchette, M., and B. Chabot. 1999. Modulation of exon skipping by high-affinity hnRNP A1-binding sites and by intron elements that repress splice site utilization. EMBO J. 18:1939–1952.
   PubMed Web of Science ®Google Scholar
• Blencowe, B. J. 2000. Exonic splicing enhancers: mechanism of action, diversity and role in human genetic diseases. Trends Biochem. Sci. 25:106–110.
   PubMed Web of Science ®Google Scholar
• Brand, K., K. A. Dugi, J. D. Brunzell, D. N. Nevin, and S. Santamarina-Fojo. 1996. A novel A→G mutation in intron I of the hepatic lipase gene leads to alternative splicing resulting in enzyme deficiency. J. Lipid Res. 37:1213–1223.
   PubMedGoogle Scholar
• Bruggenwirth, H. T., A. L. Boehmer, S. Ramnarain, M. C. Verleun-Mooijman, D. P. Satijn, J. Trapman, J. A. Grootegoed, and A. O. Brinkmann. 1997. Molecular analysis of the androgen-receptor gene in a family with receptor-positive partial androgen insensitivity: an unusual type of intronic mutation. Am. J. Hum. Genet. 61:1067–1077.
   PubMedGoogle Scholar
• Burd, C. G., and G. Dreyfuss. 1994. RNA binding specificity of hnRNP A1: significance of hnRNP A1 high-affinity binding sites in pre-mRNA splicing. EMBO J. 13:1197–1204.
   PubMed Web of Science ®Google Scholar
• Burge, C. B., T. Tuschl, and P. A. Sharp. 1999. Splicing of precursors to mRNAs by the spliceosome, p. 525–560. In R. F. Gesteland, T. R. Cech, and J. F. Atkins (ed.), The RNA world. Cold Spring Harbor Laboratory Press, New York, N.Y.
   Google Scholar
• Busslinger, M., N. Moschonas, and R. A. Flavell. 1981. Beta+ thalassemia: aberrant splicing results from a single point mutation in an intron. Cell 27:289–298.
   PubMed Web of Science ®Google Scholar
• Cáceres, J. F., T. Misteli, G. R. Screaton, D. L. Spector, and A. R. Krainer. 1997. Role of the modular domains of SR proteins in subnuclear localization and alternative splicing specificity. J. Cell Biol. 138:225–238.
   PubMed Web of Science ®Google Scholar
• Cáceres, J. F., G. R. Screaton, and A. R. Krainer. 1998. A specific subset of SR proteins shuttles continuously between the nucleus and the cytoplasm. Genes Dev. 12:55–66.
   PubMed Web of Science ®Google Scholar
• Caputi, M., and A. M. Zahler. 2001. Determination of the RNA binding specificity of the heterogeneous nuclear ribonucleoprotein (hnRNP) H/H′/F/2H9 family. J. Biol. Chem. 276:43850–43859.
   PubMed Web of Science ®Google Scholar
• Carothers, A. M., G. Urlaub, D. Grunberger, and L. A. Chasin. 1993. Splicing mutants and their second-site suppressors at the dihydrofolate reductase locus in Chinese hamster ovary cells. Mol. Cell. Biol. 13:5085–5098.
   PubMed Web of Science ®Google Scholar
• Cartegni, L., S. L. Chew, and A. R. Krainer. 2002. Listening to silence and understanding nonsense: exonic mutations that affect splicing. Nat. Rev. Genet. 3:285–298.
   PubMed Web of Science ®Google Scholar
• Chew, S. L., L. Baginsky, and I. C. Eperon. 2000. An exonic splicing silencer in the testes-specific DNA ligase III beta exon. Nucleic Acids Res. 28:402–410.
   PubMedGoogle Scholar
• Chua, K., and R. Reed. 2001. An upstream AG determines whether a downstream AG is selected during catalytic step II of splicing. Mol. Cell. Biol. 21:1509–1514.
   PubMed Web of Science ®Google Scholar
• de Baey, A., B. Fellerhoff, S. Maier, S. Martinozzi, U. Weidle, and E. H. Weiss. 1997. Complex expression pattern of the TNF region gene LST1 through differential regulation, initiation, and alternative splicing. Genomics 45:591–600.
   PubMedGoogle Scholar
• Deirdre, A., J. Scadden, and C. W. Smith. 1995. Interactions between the terminal bases of mammalian introns are retained in inosine-containing pre-mRNAs. EMBO J. 14:3236–3246.
   PubMed Web of Science ®Google Scholar
• Del Gatto, F., and R. Breathnach. 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.
   PubMedGoogle Scholar
• Fairbrother, W. G., and L. A. Chasin. 2000. Human genomic sequences that inhibit splicing. Mol. Cell. Biol. 20:6816–6825.
   PubMed Web of Science ®Google Scholar
• Fairbrother, W. G., R. F. Yeh, P. A. Sharp, and C. B. Burge. 2002. Predictive identification of exonic splicing enhancers in human genes. Science 297:1007–1013.
   PubMed Web of Science ®Google Scholar
• Fujimaru, M., A. Tanaka, K. Choeh, N. Wakamatsu, H. Sakuraba, and G. Isshiki. 1998. Two mutations remote from an exon/intron junction in the beta-hexosaminidase beta-subunit gene affect 3′-splice site selection and cause Sandhoff disease. Hum. Genet. 103:462–469.
   PubMedGoogle Scholar
• Gabellini, N. 2001. A polymorphic GT repeat from the human cardiac Na+Ca2+ exchanger intron 2 activates splicing. Eur. J. Biochem. 268:1076–1083.
   PubMedGoogle Scholar
• Graham, I. R., M. Hamshere, and I. C. Eperon. 1992. Alternative splicing of a human α-tropomyosin muscle-specific exon: identification of determining sequences. Mol. Cell. Biol. 12:3872–3882.
   PubMedGoogle Scholar
• Graveley, B. R., K. J. Hertel, and T. Maniatis. 1999. SR proteins are ‘locators’ of the RNA splicing machinery. Curr. Biol. 9:R6–R7.
   PubMed Web of Science ®Google Scholar
• Hefferon, T. W., J. D. Groman, C. E. Yurk, and G. R. Cutting. 2004. A variable dinucleotide repeat in the CFTR gene contributes to phenotype diversity by forming RNA secondary structures that alter splicing. Proc. Natl. Acad. Sci. USA 101:3504–3509.
   PubMed Web of Science ®Google Scholar
• Higashi, Y., A. Tanae, H. Inoue, T. Hiromasa, and Y. Fujii-Kuriyama. 1988. Aberrant splicing and missense mutations cause steroid 21-hydroxylase [P-450(C21)] deficiency in humans: possible gene conversion products. Proc. Natl. Acad. Sci. USA 85:7486–7490.
   PubMed Web of Science ®Google Scholar
• Ho, S. N., H. D. Hunt, R. M. Horton, J. K. Pullen, and L. R. Pease. 1989. Site-directed mutagenesis by overlap extension using the polymerase chain reaction. Gene 77:51–59.
   PubMed Web of Science ®Google Scholar
• Holzinger, I., A. de Baey, G. Messer, G. Kick, H. Zwierzina, and E. H. Weiss. 1995. Cloning and genomic characterization of LST1: a new gene in the human TNF region. Immunogenetics 42:315–322.
   PubMed Web of Science ®Google Scholar
• Howe, K. J., and M. Ares, Jr. 1997. Intron self-complementarity enforces exon inclusion in a yeast pre-mRNA. Proc. Natl. Acad. Sci. USA 94:12467–12472.
   PubMedGoogle Scholar
• Hui, J., K. Stangl, W. S. Lane, and A. Bindereif. 2003. HnRNP L stimulates splicing of the eNOS gene by binding to variable-length CA repeats. Nat. Struct. Biol. 10:33–37.
   PubMedGoogle Scholar
• Janssen, R. J., R. A. Wevers, M. Haussler, J. A. Luyten, G. C. Steenbergen-Spanjers, G. F. Hoffmann, T. Nagatsu, and L. P. Van den Heuvel. 2000. A branch site mutation leading to aberrant splicing of the human tyrosine hydroxylase gene in a child with a severe extrapyramidal movement disorder. Ann. Hum. Genet. 64:375–382.
   PubMedGoogle Scholar
• Jurka, J., and E. Zuckerkandl. 1991. Free left arms as precursor molecules in the evolution of Alu sequences. J. Mol. Evol. 33:49–56.
   PubMedGoogle Scholar
• Kan, J. L., and M. R. Green. 1999. Pre-mRNA splicing of IgM exons M1 and M2 is directed by a juxtaposed splicing enhancer and inhibitor. Genes Dev. 13:462–471.
   PubMedGoogle Scholar
• Kapitonov, V., and J. Jurka. 1996. The age of Alu subfamilies. J. Mol. Evol. 42:59–65.
   PubMed Web of Science ®Google Scholar
• Kashima, T., and J. L. Manley. 2003. A negative element in SMN2 exon 7 inhibits splicing in spinal muscular atrophy. Nat. Genet. 34:460–463.
   PubMed Web of Science ®Google Scholar
• Khan, S. G., A. Metin, E. Gozukara, H. Inui, T. Shahlavi, V. Muniz-Medina, C. C. Baker, T. Ueda, J. R. Aiken, T. D. Schneider, and K. H. Kraemer. 2003. Two essential splice lariat branchpoint sequences in one intron in a xeroderma pigmentosum DNA repair gene: mutations result in reduced XPC mRNA levels that correlate with cancer risk. Hum. Mol. Genet. 13:343–352.
   PubMedGoogle Scholar
• Krainer, A. R., G. C. Conway, and D. Kozak. 1990. The essential pre-mRNA splicing factor SF2 influences 5′ splice site selection by activating proximal sites. Cell 62:35–42.
   PubMed Web of Science ®Google Scholar
• Královičová, J., S. Houngninou-Molango, A. Krämer, and I. Vořechovský. 2004. Branch sites haplotypes that control alternative splicing. Hum. Mol. Genet. 13:3189–3202.
   PubMedGoogle Scholar
• Lehner, B., J. I. Semple, S. E. Brown, D. Counsell, R. D. Campbell, and C. M. Sanderson. 2004. Analysis of a high-throughput yeast two-hybrid system and its use to predict the function of intracellular proteins encoded within the human MHC class III region. Genomics 83:153–167.
   PubMed Web of Science ®Google Scholar
• Lei, H. 2004. Ph.D. thesis. Karolinska Institute, Stockholm, Sweden.
   Google Scholar
• Lev-Maor, G., R. Sorek, N. Shomron, and G. Ast. 2003. The birth of an alternatively spliced exon: 3′ splice-site selection in Alu exons. Science 300:1288–1291.
   PubMed Web of Science ®Google Scholar
• Makalowski, W. 2003. Genomics. Not junk after all. Science 300:1246–1247.
   PubMedGoogle Scholar
• Makalowski, W., G. A. Mitchell, and D. Labuda. 1994. Alu sequences in the coding regions of mRNA: a source of protein variability. Trends Genet. 10:188–193.
   PubMed Web of Science ®Google Scholar
• Mitchell, G. A., D. Labuda, G. Fontaine, J. M. Saudubray, J. P. Bonnefont, S. Lyonnet, L. C. Brody, G. Steel, C. Obie, and D. Valle. 1991. Splice-mediated insertion of an Alu sequence inactivates ornithine delta-aminotransferase: a role for Alu elements in human mutation. Proc. Natl. Acad. Sci. USA 88:815–819.
   PubMed Web of Science ®Google Scholar
• Mount, S. M. 1982. A catalogue of splice junction sequences. Nucleic Acids Res. 10:459–472.
   PubMed Web of Science ®Google Scholar
• Muro, A. F., M. Caputi, R. Pariyarath, F. Pagani, E. Buratti, and F. E. Baralle. 1999. Regulation of fibronectin EDA exon alternative splicing: possible role of RNA secondary structure for enhancer display. Mol. Cell. Biol. 19:2657–2671.
   PubMed Web of Science ®Google Scholar
• Nemeroff, M. E., U. Utans, A. Krämer, and R. M. Krug. 1992. Identification of cis-acting intron and exon regions in influenza virus NS1 mRNA that inhibit splicing and cause the formation of aberrantly sedimenting presplicing complexes. Mol. Cell. Biol. 12:962–970.
   PubMedGoogle Scholar
• Niksic, M., M. Romano, E. Buratti, F. Pagani, and F. E. Baralle. 1999. Functional analysis of cis-acting elements regulating the alternative splicing of human CFTR exon 9. Hum. Mol. Genet. 8:2339–2349.
   PubMedGoogle Scholar
• Raghunathan, A., R. Sivakamasundari, J. Wolenski, R. Poddar, and S. M. Weissman. 2001. Functional analysis of B144/LST1: a gene in the tumor necrosis factor cluster that induces formation of long filopodia in eukaryotic cells. Exp. Cell Res. 268:230–244.
   PubMedGoogle Scholar
• Rollinger-Holzinger, I., B. Eibl, M. Pauly, U. Griesser, F. Hentges, B. Auer, G. Pall, P. Schratzberger, D. Niederwieser, E. H. Weiss, and H. Zwierzina. 2000. LST1: a gene with extensive alternative splicing and immunomodulatory function. J. Immunol. 164:3169–3176.
   PubMedGoogle Scholar
• Si, Z., B. A. Amendt, and C. M. Stoltzfus. 1997. Splicing efficiency of human immunodeficiency virus type 1 tat RNA is determined by both a suboptimal 3′ splice site and a 10 nucleotide exon splicing silencer element located within tat exon 2. Nucleic Acids Res. 25:861–867.
   PubMedGoogle Scholar
• Siebel, C. W., L. D. Fresco, and D. C. Rio. 1992. The mechanism of somatic inhibition of Drosophila P-element pre-mRNA splicing: multiprotein complexes at an exon pseudo-5′ splice site control U1 snRNP binding. Genes Dev. 6:1386–1401.
   PubMedGoogle Scholar
• Smith, C. W. J., T. T. Chu, and B. Nadal-Ginard. 1993. Scanning and competition between AGs are involved in 3′ splice site selection in mammalian introns. Mol. Cell. Biol. 13:4939–4952.
   PubMedGoogle Scholar
• Sorek, R., G. Ast, and D. Graur. 2002. Alu-containing exons are alternatively spliced. Genome Res. 12:1060–1067.
   PubMed Web of Science ®Google Scholar
• Sorek, R., G. Lev-Maor, M. Reznik, T. Dagan, F. Belinky, D. Graur, and G. Ast. 2004. Minimal conditions for exonization of intronic sequences: 5′ splice site formation in Alu exons. Mol. Cell 14:221–231.
   PubMed Web of Science ®Google Scholar
• Staffa, A., and A. Cochrane. 1995. Identification of positive and negative splicing regulatory elements within the terminal tat-rev exon of human immunodeficiency virus type 1. Mol. Cell. Biol. 15:4597–4605.
   PubMedGoogle Scholar
• Sun, H., and L. A. Chasin. 2000. Multiple splicing defects in an intronic false exon. Mol. Cell. Biol. 20:6414–6425.
   PubMed Web of Science ®Google Scholar
• Tacke, R., and J. L. Manley. 1999. Determinants of SR protein specificity. Curr. Opin. Cell Biol. 11:358–362.
   PubMedGoogle Scholar
• Tomonaga, K., T. Kobayashi, B. J. Lee, M. Watanabe, W. Kamitani, and K. Ikuta. 2000. Identification of alternative splicing and negative splicing activity of a nonsegmented negative-strand RNA virus, Borna disease virus. Proc. Natl. Acad. Sci. USA 97:12788–12793.
   PubMedGoogle Scholar
• Udalova, I. A., S. A. Nedospasov, G. C. Webb, D. D. Chaplin, and R. L. Turetskaya. 1993. Highly informative typing of the human TNF locus using six adjacent polymorphic markers. Genomics 16:180–186.
   PubMed Web of Science ®Google Scholar
• Vořechovský, I., L. Luo, M. J. Dyer, D. Catovsky, P. L. Amlot, J. C. Yaxley, L. Foroni, L. Hammarstrom, A. D. Webster, and M. A. Yuille. 1997. Clustering of missense mutations in the ataxia-telangiectasia gene in a sporadic T-cell leukaemia. Nat. Genet. 17:96–99.
   PubMed Web of Science ®Google Scholar
• Wang, Z., M. E. Rolish, G. Yeo, V. Tung, M. Mawson, and C. B. Burge. 2004. Systematic identification and analysis of exonic splicing silencers. Cell 119:831–845.
   PubMed Web of Science ®Google Scholar
• Wentz, M. P., B. E. Moore, M. W. Cloyd, S. M. Berget, and L. A. Donehower. 1997. A naturally arising mutation of a potential silencer of exon splicing in human immunodeficiency virus type 1 induces dominant aberrant splicing and arrests virus production. J. Virol. 71:8542–8551.
   PubMedGoogle Scholar
• Yeo, G., S. Hoon, B. Venkatesh, and C. B. Burge. 2004. Variation in sequence and organization of splicing regulatory elements in vertebrate genes. Proc. Natl. Acad. Sci. USA 101:15000–15005.
   Google Scholar
• Zhang, X. H., and L. A. Chasin. 2004. Computational definition of sequence motifs governing constitutive exon splicing. Genes Dev. 18:1241–1250.
   PubMed Web of Science ®Google Scholar
• Zheng, Z. M. 2004. Regulation of alternative RNA splicing by exon definition and exon sequences in viral and mammalian gene expression. J. Biomed. Sci. 11:278–294.
   PubMed Web of Science ®Google Scholar
• Zheng, Z. M., M. Huynen, and C. C. Baker. 1998. A pyrimidine-rich exonic splicing suppressor binds multiple RNA splicing factors and inhibits spliceosome assembly. Proc. Natl. Acad. Sci. USA 95:14088–14093.
   PubMedGoogle Scholar