Splicing of a Critical Exon of Human Survival Motor Neuron Is Regulated by a Unique Silencer Element Located in the Last Intron

REFERENCES

• Bentley, D. L. 2005. Rules of engagement: co-transcriptional recruitment of pre-mRNA processing factors. Curr. Opin. Cell Biol. 17:251–256.
   PubMed Web of Science ®Google Scholar
• Black, D. L. 2003. Mechanisms of alternative pre-messenger RNA splicing. Annu. Rev. Biochem. 72:291–336.
   PubMed Web of Science ®Google Scholar
• Buratti, E., and F. E. Baralle. 2004. Influence of RNA structure on the pre-mRNA splicing process. Mol. Cell. Biol. 24:10505–10514.
   PubMed Web of Science ®Google Scholar
• Buratti, E., and F. E. Baralle. 2005. Another step forward for SELEXive splicing. Trends Mol. Med. 11:5–9.
   PubMedGoogle Scholar
• Cartegni, L., and A. R. Krainer. 2002. Disruption of an SF2/ASF-dependent exonic splicing enhancer in SMN2 causes spinal muscular atrophy in the absence of SMN1. Nat. Genet. 30:377–384.
   PubMed Web of Science ®Google Scholar
• Cartegni, L., and A. R. Krainer. 2003. Correction of disease-associated exon skipping by synthetic exon-specific activators. Nat. Struct. Biol. 10:120–125.
   PubMedGoogle Scholar
• Cartegni, L., J. Wang, Z. Zhu, M. Q. Zhang, and A. R. Krainer. 2003. ESEfinder: a web resource to identify exonic splicing enhancers. Nucleic Acids Res. 31:3568–3571.
   PubMed Web of Science ®Google Scholar
• Chen, X., L. Guo, W. Lin, and P. Xu. 2003. Expression of Tra2β isoforms is developmentally regulated in a tissue- and temporal-specific pattern. Cell Biol. Int. 27:491–496.
   PubMedGoogle Scholar
• Clark, F., and T. A. Thanaraj. 2002. Categorization and characterization of transcript-confirmed constitutively and alternatively spliced introns and exons from human. Hum. Mol. Genet. 11:451–464.
   PubMed Web of Science ®Google Scholar
• Crooke, S. T. 2004. Antisense strategies. Curr. Mol. Med. 4:465–487.
   PubMed Web of Science ®Google Scholar
• Elbashir, S. M., J. Harborth, K. Weber, and T. Tuschl. 2002. Analysis of gene function in somatic mammalian cells using small interfering RNAs. Methods 26:199–213.
   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
• Faustino, N. A., and T. A. Cooper. 2003. Pre-mRNA splicing and human disease. Genes Dev. 17:419–437.
   PubMed Web of Science ®Google Scholar
• Forte, A., M. Cipollaro, A. Cascino, and U. Galderisi. 2005. Small interfering RNAs and antisense oligonucleotides for treatment of neurological diseases. Curr. Drug Targets 6:21–29.
   PubMed Web of Science ®Google Scholar
• Garcia-Blanco, M. A., A. P. Baraniak, and E. L. Lasda. 2004. Alternative splicing in disease and therapy. Nat. Biotechnol. 22:535–546.
   PubMed Web of Science ®Google Scholar
• Graveley, B. R. 2000. Sorting out the complexity of SR protein functions. RNA 6:1197–1211.
   PubMed Web of Science ®Google Scholar
• Helmken, C., Y. Hofmann, F. Schoenen, G. Oprea, H. Raschke, S. Rudnik-Schoneborn, K. Zerres, and B. Wirth. 2003. Evidence for a modifying pathway in SMA discordant families: reduced SMN level decreases the amount of its interacting partners and Htra2-β1. Hum. Genet. 114:11–21.
   PubMed Web of Science ®Google Scholar
• Hofmann, Y., C. L. Lorson, S. Stamm, E. J. Androphy, and B. Wirth. 2000. Htra2-β1 stimulates an exonic splicing enhancer and can restore full-length SMN expression to survival motor neuron 2 (SMN2). Proc. Natl. Acad. Sci. USA 97:9618–9623.
   PubMed Web of Science ®Google Scholar
• Hofmann, Y., and B. Wirth. 2002. hnRNP-G promotes exon 7 inclusion of survival motor neuron (SMN) via direct interaction with Htra2-β1. Hum. Mol. Genet. 11:2037–2049.
   PubMed Web of Science ®Google Scholar
• Hsieh-Li, H. M., J. G. Chang, Y. J. Jong, M. H. Wu, N. M. Wang, C. H. Tsai, and H. Li. 2000. A mouse model for spinal muscular atrophy. Nat. Genet. 24:66–70.
   PubMed Web of Science ®Google Scholar
• Huang, Y., N. H. Shin, Y. Sun, and K. K. Wang. 2001. Molecular cloning and characterization of a novel caspase-3 variant that attenuates apoptosis induced by proteasome inhibition. Biochem. Biophys. Res. Commun. 283:762–769.
   PubMedGoogle Scholar
• Izquierdo, J. M., N. Majos, S. Bonnal, C. Martinez, R. Castelo, R. Guigo, D. Bilbao, and J. Valcárcel. 2005. Regulation of Fas alternative splicing by antagonistic effects of TIA-1 and PTB on exon definition. Mol. Cell 19:475–484.
   PubMed Web of Science ®Google Scholar
• Jaeger, L. B., and W. A. Banks. 2005. Transport of antisense across the blood-brain barrier. Methods Mol. Med. 106:237–251.
   PubMedGoogle 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
• Kole, R., M. Vacek, and T. Williams. 2004. Modification of alternative splicing by antisense therapeutics. Oligonucleotides 14:65–74.
   PubMedGoogle Scholar
• Kornblihtt, A. R. 2005. Promoter usage and alternative splicing. Curr. Opin. Cell Biol. 17:262–268.
   PubMed Web of Science ®Google Scholar
• Lefebvre, S., L. Burglen, S. Reboullet, O. Clermont, P. Burlet, L. Viollet, B. Benichou, C. Cruaud, P. Millasseau, M. Zeviani, D. LePaslier, F. Frezal, D. Cohen, J. Weissenbach, A. Munnich, and J. Melki. 1995. Identification and characterization of a spinal muscular atrophy-determining gene. Cell 80:1–5.
   PubMedGoogle Scholar
• Lefebvre, S., P. Burlet, Q. Liu, S. Bertrandy, O. Clermont, A. Munnich, G. Dreyfuss, and J. Melki. 1997. Correlation between severity and SMN protein level in spinal muscular atrophy. Nat. Genet. 3:265–269.
   Google Scholar
• Lim, S. R., and K. J. Hertel. 2001. Modulation of survival motor neuron pre-mRNA splicing by inhibition of alternative 3′ splice site pairing. J. Biol. Chem. 276:45476–45483.
   PubMed Web of Science ®Google Scholar
• Lorson, C. L., J. Strasswimmer, J. M. Yao, J. D. Baleja, E. Hahnen, B. Wirth, T. Le, A. H. Burghes, and E. J. Androphy. 1998. SMN oligomerization defect correlates with spinal muscular atrophy severity. Nat. Genet. 19:63–66.
   PubMed Web of Science ®Google Scholar
• Lorson, C. L., E. Hahnen, E. J. Androphy, and B. Wirth. 1999. A single nucleotide in the SMN gene regulates splicing and is responsible for spinal muscular atrophy. Proc. Natl. Acad. Sci. USA 96:6307–6311.
   PubMed Web of Science ®Google Scholar
• Lorson, C. L., and E. J. Androphy. 2000. An exonic enhancer is required for inclusion of an essential exon in the SMA-determining gene SMN. Hum. Mol. Genet. 9:259–265.
   PubMed Web of Science ®Google Scholar
• Lu, Q. L., A. Rabinowitz, Y. C. Chen, T. Yokota, H. Yin, J. Alter, A. Jadoon, G. Bou-Gharios, and T. Partridge. 2005. Systemic delivery of antisense oligoribonucleotide restores dystrophin expression in body-wide skeletal muscles. Proc. Natl. Acad. Sci. USA 102:198–203.
   PubMed Web of Science ®Google Scholar
• Mahotka, C., M. Wenzel, E. Springer, H. E. Gabbert, and C. D. Gerharz. 1999. Survivin-ΔEx3 and survivin-2B: two novel splice variants of the apoptosis inhibitor survivin with different antiapoptotic properties. Cancer Res. 59:6097–6102.
   PubMed Web of Science ®Google Scholar
• Maniatis, T., and B. Tasic. 2002. Alternative pre-mRNA splicing and proteome expansion in metazoans. Nature 418:236–243.
   PubMed Web of Science ®Google Scholar
• Mercado, P. A., Y. M. Ayala, M. Romano, E. Buratti, and F. E. Baralle. 2005. Depletion of TDP 43 overrides the need for exonic and intronic splicing enhancers in the human apoA-II gene. Nucleic Acids Res. 33:6000–6010.
   PubMed Web of Science ®Google Scholar
• Mercatante, D. R., J. L. Mohler, and R. Kole. 2002. Cellular response to an antisense-mediated shift of Bcl-x pre-mRNA splicing and antineoplastic agents. J. Biol. Chem. 277:49374–49382.
   PubMed Web of Science ®Google Scholar
• Miriami, E., H. Margalit, and R. Sperling. 2003. Conserved sequence elements associated with exon skipping. Nucleic Acids Res. 31:1974–1983.
   PubMedGoogle Scholar
• Miyajima, H., H. Miyaso, M. Okumura, J. Kurisu, and K. Imaizumi. 2002. Identification of a cis-acting element for the regulation of SMN exon 7 splicing. J. Biol. Chem. 277:23271–23277.
   PubMed Web of Science ®Google Scholar
• Miyaso, H., M. Okumura, S. Kondo, S. Higashide, H. Miyajima, and K. Imaizumi. 2003. An intronic splicing enhancer element in survival motor neuron (SMN) pre-mRNA. J. Biol. Chem. 278:15825–15831.
   PubMedGoogle Scholar
• Monani, U. R., C. L. Lorson, D. W. Parsons, T. W. Prior, E. J. Androphy, A. H. Burghes, and J. D. McPherson. 1999. A single nucleotide difference that alters splicing patterns distinguishes the SMA gene SMN1 from the copy gene SMN2. Hum. Mol. Genet. 8:1177–1183.
   PubMed Web of Science ®Google Scholar
• Monani, U. R., M. Sendtner, D. D. Coovert, D. W. Parsons, C. Andreassi, T. T. Le, S. Jablonka, B. Schrank, W. Rossol, T. W. Prior, G. E. Morris, and Burghes, A. H. 2000. The human centromeric survival motor neuron gene (SMN2) rescues embryonic lethality in Smn−/− mice and results in a mouse with spinal muscular atrophy. Hum. Mol. Genet. 9:333–339.
   PubMed Web of Science ®Google Scholar
• Nilsen, T. W. 2003. The spliceosome: the most complex macromolecular machine in the cell? Bioessays 25:1147–1149.
   PubMed Web of Science ®Google Scholar
• Nott, A., H. H. Le, and M. J. Moore. 2004. Splicing enhances translation in mammalian cells: an additional function of the exon junction complex. Genes Dev. 18:210–222.
   PubMed Web of Science ®Google Scholar
• Pagani, F., E. Buratti, C. Stuani, and F. E. Baralle. 2003. Missense, nonsense, and neutral mutations define juxtaposed regulatory elements of splicing in cystic fibrosis transmembrane regulator exon 9. J. Biol. Chem. 278:26580–26588.
   PubMedGoogle Scholar
• Pagani, F., C. Stuani, M. Tzetis, E. Kanavakis, A. Efthymiadou, S. Doudounakis, T. Casals, and F. E. Baralle. 2003. New type of disease causing mutations: the example of the composite exonic regulatory elements of splicing in CFTR exon 12. Hum. Mol. Genet. 12:1111–1120.
   PubMedGoogle Scholar
• Pagani, F., and F. E. Baralle. 2004. Genomic variants in exons and introns: identifying the splicing spoilers. Nat. Rev. Genet. 5:389–396.
   PubMed Web of Science ®Google Scholar
• Park, V. M., K. A. Kenwright, D. B. Sturtevant, and E. K. Pivnick. 1998. Alternative splicing of exons 29 and 30 in the neurofibromatosis type 1 gene. Hum. Genet. 103:382–385.
   PubMedGoogle Scholar
• Sazani, P., and R. Kole. 2003. Therapeutic potential of antisense oligonucleotides as modulators of alternative splicing. J. Clin. Investig. 112:481–486.
   PubMed Web of Science ®Google Scholar
• Singh, N. N., E. J. Androphy, and R. N. Singh. 2004. An extended inhibitory context causes skipping of exon 7 of SMN2 in spinal muscular atrophy. Biochem. Biophys. Res. Commun. 315:381–388.
   PubMed Web of Science ®Google Scholar
• Singh, N. N., E. J. Androphy, and R. N. Singh. 2004. In vivo selection reveals combinatorial controls that define a critical exon in the spinal muscular atrophy genes. RNA 10:1291–1305.
   PubMed Web of Science ®Google Scholar
• Singh, N. N., E. J. Androphy, and R. N. Singh. 2004. The regulation and regulatory activities of alternative splicing of the SMN gene. Crit. Rev. Eukaryot. Gene Expr. 14:271–285.
   PubMed Web of Science ®Google Scholar
• Skordis, L. A., M. G. Dunckley, B. Yue, I. C. Eperon, and F. Muntoni. 2003. Bifunctional antisense oligonucleotides provide a trans-acting splicing enhancer that stimulates SMN2 gene expression in patient fibroblasts. Proc. Natl. Acad. Sci. USA 100:4114–4119.
   PubMed Web of Science ®Google Scholar
• Sorek, R., and G. Ast. 2003. Intronic sequences flanking alternatively spliced exons are conserved between human and mouse. Genome Res. 13:1631–1637.
   PubMed Web of Science ®Google Scholar
• Stoss, O., T. Novoyatleva, M. Gencheva, M. Olbrich, N. Benderska, and S. Stamm. 2004. p59(fyn)-mediated phosphorylation regulates the activity of the tissue-specific splicing factor rSLM-1. Mol. Cell. Neurosci. 27:8–21.
   PubMedGoogle Scholar
• Vinogradov, S. V., E. V. Batrakova, and A. V. Kabanov. 2004. Nanogels for oligonucleotide delivery to the brain. Bioconjug. Chem. 5:50–60.
   Google Scholar
• Wan, L., D. J. Battle, J. Yong, A. K. Gubitz, S. J. Kolb, J. Wang, and G. Dreyfuss. 2005. The survival of motor neurons protein determines the capacity for snRNP assembly: biochemical deficiency in spinal muscular atrophy. Mol. Cell. Biol. 25:5543–5551.
   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
• Young, P. J., C. J. DiDonato, D. Hu, R. Kothary, E. J. Androphy, and C. L. Lorson. 2002. SRp30c-dependent stimulation of survival motor neuron (SMN) exon 7 inclusion is facilitated by a direct interaction with hTra2β1. Hum. Mol. Genet. 11:577–587.
   PubMed Web of Science ®Google Scholar
• Yu, Q., J. Guo, and J. Zhou. 2004. A minimal length between tau exon 10 and 11 is required for correct splicing of exon 10. J. Neurochem. 90:164–172.
   PubMed Web of Science ®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
• Zhang, X. H., C. S. Leslie, and L. A. Chasin. 2005. Dichotomous splicing signals in exon flanks. Genome Res. 15:768–779.
   PubMedGoogle Scholar