Effect of s on splicing of substrates

• Autorzy: Dominski Z. , Kole R.
• Języki publikacji: EN

Abstrakty

EN

We used several related pre-mRNA substrates consisting of two introns and three exons to study effects of exon sequences on in vitro splicing. By varying the sequence of the internal exon and measuring the frequency of its skipping we confirmed that 26-nucleotide exon element naturally existing in f}-globin gene and previously analysed in vivo, has a strong stimulatory effect on splicing. Sequence analysis of this element suggests that it belongs to a family of purine-rich splicing elements found in exons of several alternatively spliced pre-mRNAs. The 26-nucleotide element can efficiently function in enhancing inclusion of internal exons regardless of their size and sequence composition, suggesting that it plays a role of a general exon recognition element. The purine-rich element is dispensable in exons flanked by strong splice sites, which promote efficient inclusion of otherwise poorly recognized exons. A row of six cytidines inserted into the internal exon (GC2 mutation) initially considered to stimulate exon inclusion to a similar extent as the purine-rich element (Dominski & Kole, 1994, /. Biol. Chem. 269, 23590-23596), appears not to affect splice site selection in vitro, and in vivo it is likely to act by stabilizing mRNA that includes the internal exon against rapid cytoplasmic degradation.

Słowa kluczowe

EN

splice site selection; exon recognition sequence; exon skipping

• Wydawca: -
• Czasopismo: Acta Biochimica Polonica
• Rocznik: 1996
• Tom: 43
• Numer: 1
• Opis fizyczny: p.161-173,fig.

Twórcy

autor

Dominski Z.

• University of North Carolina, Chapel Hill, North Carolina 27599, U.S.A.

autor

Kole R.

Bibliografia

• 1. Madhani, H.D. & Guthrie, C. (1994) Dynamic RNA-RNA interactions in the spliceosome. Anna. Rev. Genet. 28, 1-26.
• 2. Moore, M.J.. Query, C.C. & Sharp, P.A. (1993) Splicing of precursors to mRNAs bv the spliceosome; in RNA World (Gesteland, R.F. & Atkins, J.F., eds.) pp. 303-358, Cold Spring Harbor Laboratory Press.
• 3. Penotti, F.K. (1991) Human pre-mRNA splicing signals. /. Vieor. Biol. 150, 385-420.
• 4. Sena pa thy, P., Shapiro, M.B. & Harris, N.L. (1990) Splice junctions, branch point sites, and exons: sequence statistics, identification, and applications to genome project- Methods Enzy- mol. 183, 252-278.
• 5. Watakabe, A., Tanaka, K. & Shimura, Y. (1993) I he role of exon sequences in splice site selection. Genes & Dev. 7,407-418.
• 6. Burtis, K.C. & Baker, B.C. (1989) Drosophila doublesex gene controls somatic sexual differen- tiation by producing alternatively spliced mRNAs encoding related sex-specific polypeptides. Cell 56. 997-1010.
• 7. Hedley, M.L. & Maniatis, T. (1991) Sex specific splicing and polyadenylation of dsxpre-mRNArequires a sequence that binds specifically to tra-2 protein in vitro. Cell 65, 579-586.
• 8. Nagoshi, R.N. & Baker, B.S. (1990) Regulation of sex-specific RNA splicing at the Drosophila doublesex gene: cis-acling mutations in exon sequences alter sex-specific RNA splicing patterns. Genes & Dev. 4,89-97.
• 9. Hoshijima, K., Inoue, K., 1 liguchi, I., Sakamoto, H. & Shimura, Y. (1991) Control of doublesex alternative splicing by transformer and transformer-2 in Drosophila. Science 252, 833-836.
• 10. Inoue, K., I loshijima, K., I liguchi, I., Sakamoto, H. & Shimura, Y. (1992) Binding of the Drosophila transformer and transformcr-2 proteins to the regulatory elements of doublesex primary transcript for sex-specific RNA processing, /'roc. Natl. Acad. Sci. U.S.A. 89, 8092-S096.
• 11. Tjan, M. & Maniatis,T. (1992) Positive control of pre-mRN Asplicing in vitro. Science 256.237-240.
• 12. Dirksen, W.P., Hampson, R.K., Sun. Q. & Rottman, F.M. (1994) A purine-rich exon sequence enhances alternative splicing ot bovine growth hormone pre-mRNA. /. Biol. Chem. 269,6431-6436.
• 13. Lavigueur, A., La Branche, H., Kornblihtt, A.R. & Chabot, B. (1993) A splicing enhancer in the human fibronectin alternate EDI exon interacts with SR proteins and stimulates U2 snRNP binding. Genes & Dev. 7, 2405-2417.
• 14. Staknis, D. & Reed, R. (1994) SR proteins promote the first specific recognition of pre-mRNA and are present together with the U1 small nuclear ribonuclcoprotein particle in a general splicing enhancer complex. Mol. Cell. Biol. 14,7670-7682.
• 15. Sun, Q., Mayeda, A., Hampson, R.H., Krainer, A.R. & Rottman, F.M. (1993) General splicing factor SF2/ASF promotes alternative splicing bv binding to exonic splicing enhancer. Gtvit*» & Dez>. 7, 2598-2608.
• 16. Tacke, R. & Manley, J.L. (1995) The human splicing factors ASF/SF2 and SC35 possess distinc, functionally significant RNA binding specificities. EM BO /. 14, 3540-3551.
• 17. Tian, H. & Kole, R. (1995) Selection of novel exon recognition elements from a pool of random sequences. Mol. Cell. Biol. 15, 6291-6298.
• 18. Dominski, Z. & Kole, R. (1994) Identification of exon sequences involved in splice site selection. /. Biol. Chew. 269,23590-23596.
• 19. Konarska, M.M., Padgett, R.A. & Sharp, P.A. (1984) Recognition of cap structure in splicing in vitro of mRNA precursors. Cell 38, 731-736.
• 20. Krainer, A.R., Maniatis, T., Ruskin, B. & Green, M.R. (1984) Normal and mutant human p-globin pre-mRNAs are faithfully and efficiently spliced in vitro. Cell 36,993-1005.
• 21. Dominski, Z. & Kole, R. (1993) Restoration of correct splicing in thalassemic pre-mRNA by antisense oligonucleotides. Proc. Natl. Acad. Sci. U.S.A. 90, 8673-8677.
• 22. Dominski, Z. &. Kole, R. (1991) Selection of splice sites in pre-mRNAs with short internal exons. Mol. Cell. Biol. 11,6075-6083.
• 23. Streuli, M. & Saito, H. (1989) Regulation of tissue-specific alternative splicing: exon- specific ns-elements govern the splicing of Ieukocvte common antigen pre-mRNA. EMBO /. 8. 787-796.
• 24. Tsai. A.Y.M., Streuli, M. & Saito, H. (1989) Integrity ot the exon 6 sequence is essential for tissue-specific alternative splicing of human Ieukocvte common antigen pre-mRNA. Mol. Cell. Biol. 9. 4550—4555.
• 25. Black. D.L. (1991) Does steric interference between splice sites block the splicing of a short c-src neuron specific exon in non-neuronal cells? Genes & Dci>. 5, 389-402.
• 26. Sterner, D. & Berget, S.M. (1993) In vivo recognition of a vertebrate mini-exon as an exon-intron-exon unit. Mol. Cell. Biol. 13, 2677-2687.
• 27. Xu. R., Teng, J. & Cooper, T. (1993) The cardiac troponin T alternative exon contains a novel purine-rich positive splicing element. Mol. Cell. Biol. 13, 3660-3674.
• 28. Ligtenberg, M.J.L., Gennissen, A.M.C., Vos, H.L. & Hilkens, J. (1991) A single nucleotide polymorphism in an exon dicatates allele dependent differential splicing of episialin mRNA. Nucleic Acids Res. 19, 297-301.
• 29. Steingrimsdottir, II., Rowley, G., Dorado. G., Cole, J. & Lehmann, A.R. (1992) Mutations which alter splicing in the human hypoxan- thine-guanosine phosphoribosvltransferase gene. Nucleic Acids Res. 20,1201-1208.
• 30. Zhuang, Y. & Weiner, A.M. (1990) The conserved dinucleohde AG of the 3' splice site may be recognized twice during in vitro splicing of mammalian mRNA precursors. Gene 90, 263-269.
• 31. Nelson, K.K. & Green, M.R. (1988) Splice site selection and ribonucleoprotein complex assembly during in vitro pre-mRNA splicing. Genes & Dev. 2, 319-329.
• 32. Siebel, P.G., Fresco, L.D. & Rio, D.C. (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. 2, 1258-1267.
• 33. Tanaka, K., Watakabe, A. & Shimura, Y. (1994) Polypurine sequences within a downstream exon function as a splicing enhancer. Mol. Cell. Biol. 14,1347-1354.
• 34. Dominski, Z. & Kole, R. (1992) Cooperation of pre-mRNA sequence elements in splice site selection. Mol. Cell. Biol. 12, 2108-2114.
• 35. Maveda, A., llelfman, D.M. & Krainer, A.R. (1993) Modulation of exon skipping and inclusion by heterogenous nuclear ribonucleoprotein A1 and pre-mRNA splicing factor SF2/ASF. Mol. Cell. Biol. 13,2993-3001.
• 36. Cooper, T.A. & Ordahl, C.P. (1989) Nucleotide substitutions within the cardiac troponin T alternative exon disrupt pre-mRNA alternative splicing. Nucleic Acids Res. 17,7905-7921.
• 37. Fu, X.-D., Katz, R.A., Skalka, A.M. & Maniatis, T. (1991) The role of branchpoint and 3'-exon sequences in the control of balanced splicing of avian retrovirus RNA. Genes & Dev. 5, 211-220.
• 38. Katz, R.A. & Skalka, A.M. (1990) Control of retroviral RNA splicing through maintenance of suboptimal processing signals. Mol. Cell. Biol. 10, 696- 704.
• 39. Robberson, B.L., Cote, G.J. & Borget, S.M. (1990) Exon definition may facilitate splice site selection in RNAs with multiple exons. Mol. Cell. Biol. 10. 84-94.
• 40. Hoffman, B.E. & Grabowski, P.J. (1992) U1 snRNP targets an essential splicing factor, U2AF65, to the 3' splice site by a network of interactions spanning the exon. Genes & Dei\ 6, 2554-2568.
• 41. Tian, M. & Maniatis, T. (1993) A splicing enhancer complex controls alternative splicing of doublesex pre-mRNA. Cell 74,105-114.
• 42. Zahler, A.M., Lane, W.S.,Stolk,J.A.& Roth,M.B. (1993) SR proteins: a conserved family of pre-mRNA splicing factors. Genes & Dev. 6, 837-847.
• 43. Aebi, M., Horning, H., Padgett, R.A., Reiser, J. & Weissmann, C. (1986) Sequence requirement for splicing of higher eukarvotic nuclear pre- mRNA. Cell 47, 555-565.
• 44. Weiss, I.M. & Liebhaber, S.A. (1995) Erythroid cell-specific mRNA stability elements in the o2-globin 3' nontranslated region. Mol. Cell. Biol. 15,2457-2465.