Control of BEK and K-SAM splice sites in alternative splicing of the fibroblast growth factor receptor 2 pre-mRNA.

The fibroblast growth factor receptor 2 gene pre-mRNA can be spliced by using either the K-SAM exon or the BEK exon. The exon chosen has a profound influence on the ligand-binding specificity of the receptor obtained. Cells make a choice between the two alternative exons by controlling use of both exons. Using fibroblast growth factor receptor 2 minigenes, we have shown that in cells normally using the K-SAM exon, the BEK exon is not used efficiently even in the absence of the K-SAM exon. This is because these cells apparently express a titratable repressor of BEK exon use. In cells normally using the BEK exon, the K-SAM exon is not used efficiently even in the absence of a functional BEK exon. Three purines in the K-SAM polypyrimidine tract are at least in part responsible for this, as their mutation to pyrimidines leads to efficient use of the K-SAM exon, while mutating the BEK polypyrimidine tract to include these purines stops BEK exon use.

[1]  A. Krainer,et al.  Modulation of exon skipping and inclusion by heterogeneous nuclear ribonucleoprotein A1 and pre-mRNA splicing factor SF2/ASF , 1993, Molecular and cellular biology.

[2]  Y. Shimura,et al.  The role of exon sequences in splice site selection. , 1993, Genes & development.

[3]  David Valle,et al.  The skipping of constitutive exons in vivo induced by nonsense mutations , 1993, Science.

[4]  P. Grabowski,et al.  U1 snRNP targets an essential splicing factor, U2AF65, to the 3' splice site by a network of interactions spanning the exon. , 1992, Genes & development.

[5]  M. Mckeown,et al.  Alternative mRNA splicing. , 1992, Annual review of cell biology.

[6]  B. S. Baker,et al.  Autoregulation and multifunctionality among trans-acting factors that regulate alternative pre-mRNA processing. , 1992, The Journal of biological chemistry.

[7]  I. Higuchi,et al.  Binding of the Drosophila transformer and transformer-2 proteins to the regulatory elements of doublesex primary transcript for sex-specific RNA processing. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[8]  M. Jaye,et al.  Fibroblast growth factor receptor tyrosine kinases: molecular analysis and signal transduction. , 1992, Biochimica et biophysica acta.

[9]  L. Naeger,et al.  Nonsense mutations inhibit splicing of MVM RNA in cis when they interrupt the reading frame of either exon of the final spliced product. , 1992, Genes & development.

[10]  T. Takeya,et al.  Tissue-specific expression of two isoforms of chicken fibroblast growth factor receptor, bek and Cek3. , 1992, Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research.

[11]  D. Black.  Activation of c-src neuron-specific splicing by an unusual RNA element in vivo and in vitro , 1992, Cell.

[12]  Y. Yarden,et al.  A confined variable region confers ligand specificity on fibroblast growth factor receptors: implications for the origin of the immunoglobulin fold. , 1992, The EMBO journal.

[13]  T. Maniatis,et al.  Positive control of pre-mRNA splicing in vitro. , 1992, Science.

[14]  Y. Yazaki,et al.  K-sam gene encodes secreted as well as transmembrane receptor tyrosine kinase. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[15]  R Kole,et al.  Selection of splice sites in pre-mRNAs with short internal exons , 1991, Molecular and cellular biology.

[16]  D. Helfman,et al.  Alternative splicing of beta-tropomyosin pre-mRNA: cis-acting elements and cellular factors that block the use of a skeletal muscle exon in nonmuscle cells. , 1991, Genes & development.

[17]  L. Williams,et al.  The human fibroblast growth factor receptor genes: a common structural arrangement underlies the mechanisms for generating receptor forms that differ in their third immunoglobulin domain , 1991, Molecular and cellular biology.

[18]  E. Brody,et al.  RNA secondary structure repression of a muscle-specific exon in HeLa cell nuclear extracts. , 1991, Science.

[19]  D. Libri,et al.  Tissue-specific splicing in vivo of the beta-tropomyosin gene: dependence on an RNA secondary structure. , 1991, Science.

[20]  E. Houssaint,et al.  Multiple mRNAs code for proteins related to the BEK fibroblast growth factor receptor. , 1991, Oncogene.

[21]  J. G. Patton,et al.  Alpha-tropomyosin mutually exclusive exon selection: competition between branchpoint/polypyrimidine tracts determines default exon choice. , 1991, Genes & development.

[22]  J. Rubin,et al.  Expression cDNA cloning of the KGF receptor by creation of a transforming autocrine loop. , 1991, Science.

[23]  Y. Courtois,et al.  Related fibroblast growth factor receptor genes exist in the human genome. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[24]  J. Manley,et al.  A protein factor, ASF, controls cell-specific alternative splicing of SV40 early pre-mRNA in vitro , 1990, Cell.

[25]  Adrian R. Krainer,et al.  The essential pre-mRNA splicing factor SF2 influences 5′ splice site selection by activating proximal sites , 1990, Cell.

[26]  Kunio Inoue,et al.  Binding of the Drosophila Sex-lethal gene product to the alternative splice site of transformer primary transcript , 1990, Nature.

[27]  R. Reed,et al.  The organization of 3' splice-site sequences in mammalian introns. , 1989, Genes & development.

[28]  M S Gelfand,et al.  Statistical analysis of mammalian pre-mRNA splicing sites. , 1989, Nucleic acids research.

[29]  M. Mckeown,et al.  Sex-specific alternative splicing of RNA from the transformer gene results from sequence-dependent splice site blockage , 1989, Cell.

[30]  L. Chasin,et al.  Nonsense mutations in the dihydrofolate reductase gene affect RNA processing , 1989, Molecular and cellular biology.

[31]  A. Weiner,et al.  UACUAAC is the preferred branch site for mammalian mRNA splicing. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[32]  M. Frohman,et al.  Rapid production of full-length cDNAs from rare transcripts: amplification using a single gene-specific oligonucleotide primer. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[33]  N. Gough.  Rapid and quantitative preparation of cytoplasmic RNA from small numbers of cells. , 1988, Analytical biochemistry.

[34]  J. Manley,et al.  The role of the polypyrimidine stretch at the SV40 early pre‐mRNA 3′ splice site in alternative splicing. , 1988, The EMBO journal.

[35]  L. Matrisian,et al.  The mRNA coding for the secreted protease transin is expressed more abundantly in malignant than in benign tumors. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[36]  E. Lane,et al.  Effects of SV40 transformation on the cytoskeleton and behavioural properties of human keratinocytes. , 1982, Cell differentiation.

[37]  T. Fleming,et al.  Determination of ligand-binding specificity by alternative splicing: two distinct growth factor receptors encoded by a single gene. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[38]  M. Green,et al.  Biochemical mechanisms of constitutive and regulated pre-mRNA splicing. , 1991, Annual review of cell biology.

[39]  B. Nadal-Ginard,et al.  Alternative splicing: a ubiquitous mechanism for the generation of multiple protein isoforms from single genes. , 1987, Annual review of biochemistry.