SR protein-mediated inhibition of CFTR exon 9 inclusion: Molecular characterization of the intronic splicing silencer

Nucleic Acids Research

Volumn 35, Issue 13, 2007, Pages 4359-4368

  Buratti, Emanuele ^a   Stuani, Cristiana ^a   De Prato, Greta ^a   Baralle, Francisco E ^a  

^a INTERNATIONAL CENTRE FOR GENETIC ENGINEERING AND BIOTECHNOLOGY   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

ANTISENSE OLIGONUCLEOTIDE; CELL PROTEIN; GENE PRODUCT; PROTEIN ASF; PROTEIN SF2; PROTEIN SR; PROTEIN SRP40; TRANSMEMBRANE CONDUCTANCE REGULATOR; UNCLASSIFIED DRUG; NUCLEAR PROTEIN; RNA BINDING PROTEIN; SERINE ARGININE RICH SPLICING PROTEINS; SERINE-ARGININE-RICH SPLICING PROTEINS;

AMINO ACID SEQUENCE; ARTICLE; BINDING SITE; CONTROLLED STUDY; EXON; GENE MAPPING; HUMAN; HUMAN CELL; INTRON; MOLECULAR MECHANICS; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN BINDING; PROTEIN FUNCTION; RNA SPLICING; SILENCER GENE; GENETICS; HELA CELL; METABOLISM; MOLECULAR GENETICS; NUCLEOTIDE SEQUENCE; REGULATORY RNA SEQUENCE; TUMOR CELL LINE;

BASE SEQUENCE; BINDING SITES; CELL LINE, TUMOR; CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR; EXONS; HELA CELLS; HUMANS; INTRONS; MOLECULAR SEQUENCE DATA; NUCLEAR PROTEINS; OLIGONUCLEOTIDES, ANTISENSE; REGULATORY SEQUENCES, RIBONUCLEIC ACID; RNA SPLICING; RNA-BINDING PROTEINS;

EID: 34547830368     PISSN: 03051048     EISSN: 13624962     Source Type: Journal    
DOI: 10.1093/nar/gkm444     Document Type: Article

References (78)

1. Disset,A., Michot,C., Harris,A., Buratti,E., Claustres,M. and Tuffery-Giraud,S. (2005) A T3 allele in the CFTR gene exacerbates exon 9 skipping in vas deferens and epididymal cell lies and is associated with Congenital Bilateral Absence of Vas Deferens (CBAVD). Hum. Mutat., 25, 72-81.
2. Groman,J.D., Hefferon,T.W., Casals,T., Bassas,L., Estivill,X., Des Georges,M., Guittard,C., Koudova,M., Fallin,M.D. et al. (2004) Variation in a repeat sequence determines whether a common variant of the cystic fibrosis transmembrane conductance regulator gene is pathogenic or benign. Am. J. Hum. Genet., 74, 176-179.
3. Cuppens,H., Lin,W., Jaspers,M., Costes,B., Teng,H., Vankeerberghen,A., Jorissen,M., Droogmans,G., Reynaert,I. et al. (1998) Polyvariant mutant cystic fibrosis transmembrane conductance regulator genes. The polymorphic (Tg)m locus explains the partial penetrance of the T5 polymorphism as a disease mutation. J. Clin. Invest., 101, 487-496.
4. Rave-Harel,N., Kerem,E., Nissim-Rafinia,M., Madjar,I., Goshen,R., Augarten,A., Rahat,A., Hurwitz,A., Darvasi,A. et al. (1997) The molecular basis of partial penetrance of splicing mutations in cystic fibrosis. Am. J. Hum. Genet., 60, 87-94.
5. Chu,C.S., Trapnell,B.C., Curristin,S., Cutting,G.R. and Crystal,R.G. (1993) Genetic basis of variable exon 9 skipping in cystic fibrosis transmembrane conductance regulator mRNA. Nat. Genet., 3, 151-156.
6. Buratti,E., Dork,T., Zuccato,E., Pagani,F., Romano,M. and Baralle,F.E. (2001) Nuclear factor TDP-43 and SR proteins promote in vitro and in vivo CFTR exon 9 skipping. EMBO J., 20, 1774-1784.
7. Niksic,M., Romano,M., Buratti,E., Pagani,F. and Baralle,F.E. (1999) Functional analysis of cis-acting elements regulating the alternative splicing of human CFTR exon 9. Hum. Mol. Genet., 8, 2339-2349.
8. Hefferon,T.W., Broackes-Carter,F.C., Harris,A. and Cutting,G.R. (2002) Atypical 5′ splice sites cause CFTR exon 9 to be vulnerable to skipping. Am. J. Hum. Genet., 71, 2.
9. Zuccato,E., Buratti,E., Stuani,C., Baralle.F.E. and Pagani,F. (2004) An intronic polypyrimidine-rich element downstream of the donor site modulates cystic fibrosis transmembrane conductance regulator exon 9 alternative splicing. J. Biol. Chem., 279, 16980-16988.
10. Pagani,F., Buratti,E., Stuani,C. and Baralle,F.E. (203) Missense, nonsense, and neutral mutations define juxtaposed regulatory elements of splicing in cystic fibrosis transmembrane regulator exon 9. J. Biol. Chem., 278, 26580-26588.
11. Pagani,F., Buratti,E., Stuani,C, Romano,M., Zuccato,E., Niksic,M., Giglio,L., Faraguna,D. and Baralle,F.E. (2000) Splicing factors induce rystic fibrosis transmembrane regulator exon 9 skipping through a non-evolutionary conserved intronic element. J. Biol. Chem., 275, 21041-21047.
12. Buratti,E., Brindisi,A., Pagani,F. and Baralle,F.E. (2004) Nuclear factor TDP-43 binds to the polymorphic TG repeats in CFTR intron 8 and causes skipping of exon 9: A functional link with disease penetrance. Am. J. Hum. Genet., 74, 1322-1325.
13. Buratti,E., Brindisi,A., Giombi,M., Tisminetzky,S., Ayala,Y.M. and Baralle,F.E. (2005) TDP-43 Binds Heterogeneous Nuclear Ribonucleoprotein A/B through Its C-terminal Tail: An important region for the inhibition of cystic fibrosis transmembrane conductance regulator exon 9 splicing. J. Biol. Chem., 280, 37572-37584.
14. Bourgeois,C.F., Lejeune,F. and Stevenin,J. (2004) Broad specificity of SR (serine/arginine) proteins in the regulation of alternative splicing of pre-messenger RNA. Prog. Nucleic Acid Res. Mol. Biol., 78 37-88.
15. Fu,X.D. (1995) The superfamily of arginine/serine-rich splicing factors. RANA, 1, 663-680.
16. Sanford,J.R., Ellis,J. and Caceres,J.F. (2005) Multiple roles of arginine/serine-rich splicing factors in RNA processing. Biochem. Soc. Trans., 33, 443-446.
17. Graveley,B.R. (2000) Sorting out the complexity of SR protein functions. RNA, 6, 1197-1211.
18. Graveley,B.R., Hertel,K.J. and Maniatis,T. (1999) SR proteins are 'locators' of the RNA splicing machinery. Curr. Biol., 9, R6-R7.
19. Hertel,K.J. and Graveley,B.R. (2005) RS domains contact the pre-mRNA throughout spliceosome assembly. Trends Biochem. Sci., 30, 115-118.
20. Shen,H. and Green,M.R. (2004) A pathway of sequential arginine-serine-rich domain-splicing signal interactions during mammalian splicoeosome assembly. Mol. Cell, 16, 363-373.
21. Shen,H., Kan,J.L. and Green,M.R. (2004) Arginine-serine-rich domains bound at splicing enhancers contact the branchpoint to promote prespliceosome assembly. Mol. Cell, 13, 367-376.
22. Tacke,R. and Manley,J.L. (1999) Determinants of SR protein specificity. Curr. Opin. Cell. Biol., 11, 358-362.
23. Ram,O. and Ast,G. (2007) SR proteins: A foot on the exon before the transition from intron to exon definition. Trends Genet., 23 5-7.
24. Webb,C.J., Romfo,C.M., van Heeckeren,W.J. and Wise,J.A. (2005) Exonic splicing enhancers in fission yeast: Functional conservation demonstrates an early evolutionary origin. Genes Dev., 19, 242-254.
25. Li,X. and Manley,J.L. (2005) New talents for an old acquaintance: The SR protein splicing factor ASF/SF2 functions in the maintenance of genome stability. Cell Cycle, 4, 1706-1108.
26. Li,X., Wang,J. and Manley,J.L. (2005) Loss of splicing factor ASF/SF2 induces G2 cell cycle arrest and apoptosis, but inhibits internucleosomal DNA fragmentation. Genes Dev., 19, 2705-2714.
27. Li,X. and Manley,J.L. (2005) Inactivation of the SR protein splicing factor ASF/SF2 results in genomic instability. Cell, 122, 365-378.
28. Huang,Y. and Steitz,J.A. (2001) Splicing factors SRp20 and 9G8 promote the nucleocytoplasmic export of mRNA. Mol. Cell, 7, 899-905.
29. Huang,Y., Gattoni,R., Stevenin,J. and Steitz,J.A. (2003) SR splicing factors serve as adapter proteins for TAP-dependent mRNA export. Mol. Cell, 11, 837-843.
30. Huang,Y. and Steitz,J.A. (2005) SRprises along a messenger's journey. Mol. Cell, 17, 613-615.
31. Huang,Y., Yario,T.A. and Steitz,J.A. (2004) A molecular link between SR protein dephosphorylation and mRNA export. Proc. Natl Acad. Sci. USA 101, 9666-9670.
32. Zhang,Z. and Krainer,A.R. (2004) Involvement of SR proteins in mRNA surveillance. Mol. Cell, 16, 597-607.
33. Sanford,J.R., Gray,N.K., Beckmann,K. and Caceres,J.F. (2004) A novel role for shuttling SR proteins in mRNA translation. Genes Dev., 18, 755-768.
34. Blaustein,M., Pelisch,F., Tanos,T., Munoz,M.J., Wengier,D., Quadrana,L., Sanford,J.R., Muschietti,J.P., Kornblihtt,A.R. et al. (2005) Concerted regulation of nuclear and cytoplasmic activities of SR proteins by AKT. Nat. Struct. Mol. Biol., 12, 1037-1044.
35. Blencowe,B.J. (2000) Exonic splicing enhancers: Mechanism of action, diversity and role in human genetic diseases. Trends Biochem. Sci. 25, 106-110.
36. Ladd,A.N. and Cooper,T.A. (2002) Finding signals that regulate alternative splicing in the post-genomic era. Genome Biol., 3 reviews0008.
37. 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.
38. Smith,C.W. and Valcarcel,J. (2000) Alternative pre-mRNA splicing: The logic of combinatorial control. Trends Biochem. Sci., 25, 381-388.
39. Zhu,J., Mayeda,A. and Krainer,A.R. (2001) Exon identity established through differential antagonism between exonic splicing silencer-bound hnRNP A1 and enhancer-bound SR proteins. Mol. Cell, 8, 1351-1361.
40. Fu,X.D. (2004) Towards a splicing code. Cell, 119, 736-738.
41. Matlin,A.J.,Clark,F. and Smith,C.W. (2005) Understanding alternative splicing: Towards a cellular code. Nat. Rev. Mol. Cell. Biol., 6, 386-398.
42. Lavigueur,A., La Branche,H., Kornblihtt,A.R. and 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.
43. Eperon,I.C., Ireland,D.C., Smith,R.A., Mayeda,A. and Krainer,A.R. (1993) Pathways for selection of 5′ splice sites by U1 snRNPs and SF2/ASF. EMBO J., 12, 3607-3617.
44. Cartegni,L., Chew,S.L. and Krainer,A.R. (2002) Listening to silence and understanding nonsense: Exonic mutations that affect splicing. Nat. Rev. Genet., 3, 285-298.
45. Tarn,W.Y. and Steitz,J.A. (1994) SR proteins can compensate for the loss of U1 snRNP functions in vitro. Genes Dev., 8, 2704-2717.
46. Crispino,J.D., Blencowe,B.J. and Sharp,P.A. (1994) Complementation by SR proteins of pre-mRNA splicing reactions depleted of U1 snRNP. Science 265, 1866-1869.
47. Liu,H.X., Zhang,M. and Krainer,A.R. (1998) Identification of functional exonic splicing enhancer motifs recognized by individual SR proteins. Genes Dev., 12, 1998-2012.
48. Cazalla,D., Zhu,J., Manche,L., Huber,E., Krainer,A.R. and Caceres,J.F. (2002) Nuclear export and retention signals in the RS domain of SR proteins. Mol. Cell. Biol., 22, 6871-6882.
49. Shin,C., Feng,Y. and Manley,J.L. (2004) Dephosphorylated SRp38 acts as a splicing repressor in response to heat shock. Nature, 427, 553-558.
50. Shin,C. and Manley,J.L. (2002) The SR protein SRp38 represses splicing in M phase cells. Cell, 111, 407-417.
51. Nilsen,T.W. (2004) Too hot to splice. Nat. Struct. Mol. Biol., 11, 208-209.
52. Li,Q., Zhao,H., Jiang,L., Che,Y., Dong,C., Wang,L., Wang,J. and Liu,L. (2002) An SR-protein induced by HSVI binding to cells functioning as a splicing inhibitor of viral pre-mRNA. J. Mol. Biol., 316, 887-894.
53. Simard,M.J. and Chabot,B. (2002) SRp30c is a repressor of 3′ splice site utilization. Mol. Cell. Biol., 22, 4001-4010.
54. ten Dam,G.B., Zilch,C.F., Wallace,D., Wieringa,B., Beverley,P.C., Poels,L.G. and Screaton,G.R. (2000) Regulation of alternative splicing of CD45 by antagonistic effects of SR protein splicing factors. J. Immunol., 164, 5287-5295.
55. Wang,Y., Wang,J., Gao,L., Lafyatis,R., Stamm,S. and Andreadis,A. (2005) Tau exons 2 and 10, which are misregulated in neurodegenerative diseases, are partly regulated by silencers which bind a SRp30c.SRp55 complex that either recruits or antagonizes htra2beta1. J. Biol. Chem., 280, 14230-14239.
56. Aznarez,I., Chan,E.M., Zielenski,J., Blencowe,B.J. and Tsui,L.C. (2003) Characterization of disease-associated mutations affecting an exonic splicing enhancer and two cryptic splice sites in exon 13 of the cystic fibrosis transmembrane conductance regulator gene. Hum. Mol. Genet. 12, 2031-2040.
57. Gallego,M.E., Gattoni,R., Stevenin,J., Marie,J. and 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.
58. Kanopka.A., Muhlemann,O. and Akusjarvi,G. (1996) Inhibition by SR proteins of splicing of a regulated adenovirus pre- mRNA. Nature, 381, 535-538.
59. McNally,L.M. and McNally,M.T. (1998) An RNA splicing enhancer-like sequence is a component of a splicing inhibitor element from Rous sarcoma virus. Mol. Cell. Biol., 18, 3103-3111.
60. McNally,L.M. and McNally,M.T. (1999) U1 small nuclear ribonucleoprotein and splicing inhibition by the rous sarcoma virus negative regulator of splicing element. J. Virol., 73, 2385-2393.
61. Nissim-Rafinia,M., Chiba-Falek,O., Sharon,G., Boss,A. and Kerem,B. (2000) Cellular and viral splicing factors can modify the splicing pattern of CFTR transcripts carrying splicing mutations. Hum. Mol. Genet., 9, 1711-1778.
62. Ayala,Y.M., Pagani,F. and Baralle,F.E. (2006) TDP43 depletion rescues aberrant CFTR exon 9 skipping, FEBS Lett., 580, 1339-1344.
63. Buratti,E., Muro,A.F., Giombi,M, Gherbassi,D., Iaconcig,A. and Baralle F.E. (2004) RNA folding affects the recruitment of SR proteins by mouse and human polypurinic enhancer elements in the fibronectin EDA exon. Mol. Cell. Biol., 24, 1387-1400.
64. Mercado,P.A., Ayala,Y.M., Romano,M., Buratti,E. and Baralle,F.E. (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.
65. Woertel,G. and Bindereif,A. (2001) In vitro selection of exonic splicing enhancer sequences: Identification of novel CD44 enhancers. Nucleic Acids Res., 29, 3204-3211.
66. Tanaka,K., Watakabe,A. and Shimura,Y. (1994) Polypurine sequences within a downstream exon function as a splicing enhancer. Mol. Cell. Biol. 14, 1347-1354.
67. Reese,M.G., Eeckman,F.H., Kulp,D. and Haussler,D. (1997) Improved splice site detection in Genie. J. Comput. Biol., 4, 311-323.
68. Stickeler,E., Fraser,S.D., Honig,A., Chen,A.L., Berget,S.M. and Cooper,T.A. (2001) The RNA binding protein YB-1 binds A/C-rich exon enhancers and stimulates splicing of the CD44 alternative exon v4. EMBO J., 20, 3821-3830.
69. Simard,M.J. and Chabot,B. (2000) Control of hnRNP A1 alternative splicing: An intron element represses use of the common 3′ splice site. Mol. Cell. Biol., 20, 7353-7362.
70. Dauksaite,V. and 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.
71. McNally,L.M. and McNally,M.T. (1996) SR protein splicing factors interact with the Rous sarcoma virus negative regulator of splicing element. J. Virol., 70, 1163-1172.
72. McNally,L.M., Yee,L. and McNally,M.T. (2004) Two regions promote U11 small nuclear ribonucleoprotein particle binding to a retroviral splicing inhibitor element (negative regulator of splicing). J. Biol. Chem., 279, 38201-38208.
73. Fogel,B.L. and McNally,M.T. (2000) A cellular protein, hnRNP H, binds to the negative regulator of splicing element from Rous sarcoma virus. J. Biol. Chem., 275, 32371-32378.
74. Fogel,B.L., McNally,L.M. and McNally,M.T. (2002) Efficient polyadenylation of Rous sarcoma virus RNA requires the negative regulator of splicing element. Nucleic Acids Res., 30, 810-817.
75. Dye,M.J., Gromak,N. and Proudfoot,N.J. (2006) Exon tethering in transcription by RNA polymerase II. Mol. Cell, 21, 849-859.
76. Buratti,E., Baralle,M. and Baralle,F.E. (2006) Defective splicing, disease and therapy: Searching for master checkpoints in exon definition. Nucleic Acids Res., 34, 3494-3510.
77. Garcia-Blanco,M.A. (2005) Making antisense of splicing. Curr. Opin. Mol. Ther., 7, 476-482.
78. Wilton,S.D. and Fletcher,S. (2005) RNA splicing manipulation: Strategies to modify gene expression for a variety of therapeutic outcomes. Curr. Gene. Ther., 5, 467-483.