Artículo

Estamos trabajando para incorporar este artículo al repositorio
Consulte el artículo en la página del editor
Consulte la política de Acceso Abierto del editor

Abstract:

Alternative splicing is an important mechanism for controlling gene expression. It allows large proteomic complexity from a limited number of genes. An interplay of cis-acting sequences and trans-acting factors modulates the splicing of regulated exons. Here, we discuss the roles of the SR and hnRNP families of proteins in this process. We also focus on the role of the transcriptional machinery in the regulation of alternative splicing, and on those alterations of alternative splicing that lead to human disease.

Registro:

Documento: Artículo
Título:Alternative splicing: Multiple control mechanisms and involvement in human disease
Autor:Cáceres, J.F.; Kornblihtt, A.R.
Filiación:MRC Human Genetics Unit, Western General Hospital, Edinburgh EH4 2XU, United Kingdom
Laboratorio de Fisiología y Biología Molecular, Departamento de Fisiologia, Universidad de Buenos Aires, Pabellón 2, (1428) Buenos Aires, Argentina
Palabras clave:cis acting element; RNA; RNA binding protein; trans acting factor; transcription factor; alternative RNA splicing; cystic fibrosis; exon; gene expression; gene expression regulation; gene mutation; gene number; genetic code; genetic disorder; hemophilia A; human; Huntington chorea; Marfan syndrome; missense mutation; molecular model; myotonic dystrophy; nonhuman; nonsense mutation; nucleotide repeat; pathophysiology; point mutation; priority journal; promoter region; protein expression; protein family; protein function; protein motif; review; RNA binding; RNA processing; RNA transcription; Sandhoff disease; single nucleotide polymorphism; tissue specificity; Alternative Splicing; Animals; Gene Expression Regulation; Genetic Predisposition to Disease; Heterogeneous-Nuclear Ribonucleoproteins; Humans; Multigene Family; Ribonucleoproteins; RNA Splice Sites; Trans-Activators; Transcription, Genetic
Año:2002
Volumen:18
Número:4
Página de inicio:186
Página de fin:193
DOI: http://dx.doi.org/10.1016/S0168-9525(01)02626-9
Título revista:Trends in Genetics
Título revista abreviado:Trends Genet.
ISSN:01689525
CODEN:TRGEE
CAS:Heterogeneous-Nuclear Ribonucleoproteins; Ribonucleoproteins; RNA Splice Sites; Trans-Activators
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01689525_v18_n4_p186_Caceres

Referencias:

  • Black, D.L., Protein diversity from alternative splicing: A challenge for bioinformatics and post-genome biology (2000) Cell, 103, pp. 367-370
  • Graveley, B.R., Alternative splicing: Increasing diversity in the proteomic world (2001) Trends Genet., 17, pp. 100-107
  • Kramer, A., The structure and function of proteins involved in mammalian pre-mRNA splicing (1996) Annu. Rev. Biochem., 65, pp. 367-409
  • Dreyfuss, G., hnRNP proteins and the biogenesis of mRNA (1993) Annu. Rev. Biochem., 62, pp. 289-321
  • Smith, C.W., Valcarcel, J., Alternative pre-mRNA splicing: The logic of combinatorial control (2000) Trends Biochem. Sci., 25, pp. 381-388
  • Berget, S.M., Exon recognition in vertebrate splicing (1995) J. Biol. Chem., 270, pp. 2411-2414
  • Horowitz, D.S., Krainer, A.R., Mechanisms for selecting 5′ splice sites in mammalian pre-mRNA splicing (1994) Trends Genet., 10, pp. 100-106
  • Fu, X.D., The superfamily of arginine/serine-rich splicing factors (1995) RNA, 1, pp. 663-680
  • Graveley, B.R., Sorting out the complexity of SR protein functions (2000) RNA, 6, pp. 1197-1211
  • Tacke, R., Manley, J.L., Determinants of SR protein specificity (1999) Curr. Opin. Cell Biol., 11, pp. 358-362
  • Wu, J.Y., Maniatis, T., Specific interactions between proteins implicated in splice site selection and regulated alternative splicing (1993) Cell, 75, pp. 1061-1070
  • Blencowe, B.J., Exonic splicing enhancers: Mechanism of action, diversity and role in human genetic diseases (2000) Trends Biochem. Sci., 25, pp. 106-110
  • Mayeda, A., Krainer, A.R., Regulation of alternative pre-mRNA splicing by hnRNP A1 and splicing factor SF2 (1992) Cell, 68, pp. 365-375
  • Caceres, J.F., Regulation of alternative splicing in vivo by overexpression of antagonistic splicing factors (1994) Science, 265, pp. 1706-1709
  • Yang, X., The A1 and A1B proteins of heterogeneous nuclear ribonucleoparticles modulate 5′ splice site selection in vivo (1994) Proc. Natl. Acad. Sci. U. S. A., 91, pp. 6924-6928
  • Gallego, M.E., The SR splicing factors ASF/SF2 and SC35 have antagonistic effects on intronic enhancer-dependent splicing of the beta-tropomyosin alternative exon 6A (1997) EMBO J., 16, pp. 1772-1784
  • Jumaa, H., Nielsen, P.J., The splicing factor SRp20 modifies splicing of its own mRNA and ASF/SF2 antagonizes this regulation (1997) EMBO J., 16, pp. 5077-5085
  • Eperon, I.C., Selection of alternative 5′ splice sites: Role of U1 snRNP and models for the antagonistic effects of SF2/ASF and hnRNP A1 (2000) Mol. Cell. Biol., 20, pp. 8303-8318
  • Chabot, B., An intron element modulating 5′ splice site selection in the hnRNP A1 pre-mRNA interacts with hnRNP A1 (1997) Mol. Cell. Biol., 17, pp. 1776-1786
  • Longman, D., Multiple interactions between SRm160 and SR family proteins in enhancer-dependent splicing and development of C. elegans (2001) Curr. Biol., 11, pp. 1923-1933
  • Hastings, M.L., Krainer, A.R., Pre-mRNA splicing in the new millennium (2001) Curr. Opin. Cell Biol., 13, pp. 302-309
  • Zhu, J., Exon identity established through differential antagonism between exonic splicing silencer-bound hnRNP A1 and enhancer-bound SR proteins (2001) Mol. Cell, 8, pp. 1351-1361
  • Zahler, A.M., Distinct functions of SR proteins in alternative pre-mRNA splicing (1993) Science, 260, pp. 219-222
  • Hanamura, A., Regulated tissue-specific expression of antagonistic pre-mRNA splicing factors (1998) RNA, 4, pp. 430-444
  • Wang, J., Targeted disruption of an essential vertebrate gene: ASF/SF2 is required for cell viability (1996) Genes Dev., 10, pp. 2588-2599
  • Jumaa, H., Blastocyst formation is blocked in mouse embryos lacking the splicing factor SRp20 (1999) Curr. Biol., 9, pp. 899-902
  • Wang, H.Y., SC35 plays a role in T cell development and alternative splicing of CD45 (2001) Mol. Cell, 7, pp. 331-342
  • Ring, H.Z., Lis, J.T., The SR protein B52/SRp55 is essential for Drosophila development (1994) Mol. Cell. Biol., 14, pp. 7499-7506
  • Peng, X., Mount, S.M., Genetic enhancement of RNA-processing defects by a dominant mutation in B52, the Drosophila gene for an SR protein splicing factor (1995) Mol. Cell. Biol., 15, pp. 6273-6282
  • Hoffman, B.E., Lis, J.T., Pre-mRNA splicing by the essential Drosophila protein B52: Tissue and target specificity (2000) Mol. Cell. Biol., 20, pp. 181-186
  • Longman, D., Functional characterization of SR and SR-related genes in Caenorhabditis elegans (2000) EMBO J., 19, pp. 1625-1637
  • Kawano, T., Unique and redundant functions of SR proteins, a conserved family of splicing factors, in Caenorhabditis elegans development (2000) Mech. Dev., 95, pp. 67-76
  • Valcarcel, J., Gebauer, F., Post-transcriptional regulation: The dawn of PTB (1997) Curr. Biol., 7, pp. R705-R708
  • Wollerton, M.C., Differential alternative splicing activity of isoforms of polypyrimidine tract binding protein (PTB) (2001) RNA, 7, pp. 819-832
  • Ladd, A.N., The CELF family of RNA binding proteins is implicated in cell-specific and developmentally regulated alternative splicing (2001) Mol. Cell. Biol., 21, pp. 1285-1296
  • Grabowski, P.J., Black, D.L., Alternative RNA splicing in the nervous system (2001) Prog. Neurobiol., 65, pp. 289-308
  • Stamm, S., A sequence compilation and comparison of exons that are alternatively spliced in neurons (1994) Nucleic Acids Res., 22, pp. 1515-1526
  • Jensen, K.B., Nova-1 regulates neuron-specific alternative splicing and is essential for neuronal viability (2000) Neuron, 25, pp. 359-371
  • Polydorides, A.D., A brain-enriched polypyrimidine tract-binding protein antagonizes the ability of Nova to regulate neuron-specific alternative splicing (2000) Proc. Natl. Acad. Sci. U. S. A., 97, pp. 6350-6355
  • Markovtsov, V., Cooperative assembly of an hnRNP complex induced by a tissue-specific homolog of polypyrimidine tract binding protein (2000) Mol. Cell. Biol., 20, pp. 7463-7479
  • Bentley, D., Coupling RNA polymerase II transcription with pre-mRNA processing (1999) Curr. Opin. Cell Biol., 11, pp. 347-351
  • Hirose, Y., Manley, J.L., RNA polymerase II and the integration of nuclear events (2000) Genes Dev., 14, pp. 1415-1429
  • Proudfoot, N., Connecting transcription to messenger RNA processing (2000) Trends Biochem. Sci., 25, pp. 290-293
  • Misteli, T., The dynamics of a pre-mRNA splicing factor in living cells (1997) Nature, 387, pp. 523-527
  • Misteli, T., Spector, D.L., RNA polymerase II targets pre-mRNA splicing factors to transcription sites in vivo (1999) Mol. Cell, 3, pp. 697-705
  • McCracken, S., The C-terminal domain of RNA polymerase II couples mRNA processing to transcription (1997) Nature, 385, pp. 357-361
  • Cramer, P., Functional association between promoter structure and transcript alternative splicing (1997) Proc. Natl. Acad. Sci. U. S. A., 94, pp. 11456-11460
  • Cramer, P., Coupling of transcription with alternative splicing: RNA pol II promoters modulate SF2/ASF and 9G8 effects on an exonic splicing enhancer (1999) Mol. Cell, 4, pp. 251-258
  • Ge, H., A novel transcriptional coactivator, p52, functionally interacts with the essential splicing factor ASF/SF2 (1998) Mol. Cell, 2, pp. 751-759
  • Lai, M.C., A human papillomavirus E2 transcriptional activator. The interactions with cellular splicing factors and potential function in pre-mRNA processing (1999) J. Biol. Chem., 274, pp. 11832-11841
  • Davies, R.C., WT1 interacts with the splicing factor U2AF65 in an isoform-dependent manner and can be incorporated into spliceosomes (1998) Genes Dev., 12, pp. 3217-3225
  • Monsalve, M., Direct coupling of transcription and mRNA processing through the thermogenic coactivator PGC-1 (2000) Mol. Cell, 6, pp. 307-316
  • Nayler, O., SAF-B protein couples transcription and pre-mRNA splicing to SAR/MAR elements (1998) Nucleic Acids Res., 26, pp. 3542-3549
  • Morris, D.P., Greenleaf, A.L., The splicing factor, Prp40, binds the phosphorylated carboxyl-terminal domain of RNA polymerase II (2000) J. Biol. Chem., 275, pp. 39935-39943
  • Myers, J.K., Phosphorylation of RNA polymerase II CTD fragments results in tight binding to the WW domain from the yeast prolyl isomerase Ess1 (2001) Biochemistry, 40, pp. 8479-8486
  • Carty, S.M., Protein-interaction modules that organize nuclear function: FF domains of CA150 bind the phosphoCTD of RNA polymerase II (2000) Proc. Natl. Acad. Sci. U. S. A., 97, pp. 9015-9020
  • Yuryev, A., The C-terminal domain of the largest subunit of RNA polymerase II interacts with a novel set of serine/arginine-rich proteins (1996) Proc. Natl. Acad. Sci. U. S. A., 93, pp. 6975-6980
  • Patturajan, M., A nuclear matrix protein interacts with the phosphorylated C-terminal domain of RNA polymerase II (1998) Mol. Cell. Biol., 18, pp. 2406-2415
  • Kadener, S., Antagonistic effects of T-Ag and VP16 reveal a role for RNA pol II elongation on alternative splicing (2001) EMBO J., 20, pp. 5759-5768
  • Eperon, L.P., Effects of RNA secondary structure on alternative splicing of pre-mRNA: Is folding limited to a region behind the transcribing RNA polymerase? (1988) Cell, 54, pp. 393-401
  • Roberts, G.C., Co-transcriptional commitment to alternative splice site selection (1998) Nucleic Acids Res., 26, pp. 5568-5572
  • Krawczak, M., The mutational spectrum of single base-pair substitutions in mRNA splice junctions of human genes: Causes and consequences (1992) Hum. Genet., 90, pp. 41-54
  • Maquat, L.E., Carmichael, G.G., Quality control of mRNA function (2001) Cell, 104, pp. 173-176
  • Iborra, F.J., Coupled transcription and translation within nuclei of mammalian cells (2001) Science, 293, pp. 1139-1142
  • Liu, H.X., A mechanism for exon skipping caused by nonsense or missense mutations in BRCA1 and other genes (2001) Nat. Genet., 27, pp. 55-58
  • Buratti, E., Nuclear factor TDP-43 and SR proteins promote in vitro and in vivo CFTR exon 9 skipping (2001) EMBO J., 20, pp. 1774-1784
  • Philips, A.V., Disruption of splicing regulated by a CUG-binding protein in myotonic dystrophy (1998) Science, 280, pp. 737-741
  • Savkur, R.S., Aberrant regulation of insulin receptor alternative splicing is associated with insulin resistance in myotonic dystrophy (2001) Nat. Genet., 29, pp. 40-47
  • Llewellyn, D.H., Acute intermittent porphyria caused by defective splicing of porphobilinogen deaminase RNA: A synonymous codon mutation at -22 bp from the 5′ splice site causes skipping of exon 3 (1996) J. Med. Genet., 33, pp. 437-438
  • Mazoyer, S., A BRCA1 nonsense mutation causes exon skipping (1998) Am. J. Hum. Genet., 62, pp. 713-715
  • Vuillaumier-Barrot, S., Characterization of the 415G→A (E139K) PMM2 mutation in carbohydrate-deficient glycoprotein syndrome type Ia disrupting a splicing enhancer resulting in exon 5 skipping (1999) Hum. Mutat., 14, pp. 543-544
  • Chen, W., Silent nucleotide substitution in the sterol 27-hydroxylase gene (CYP 27) leads to alternative pre-mRNA splicing by activating a cryptic 5′ splice site at the mutant codon in cerebrotendinous xanthomatosis patients (1998) Biochemistry, 37, pp. 4420-4428
  • Pousi, B., A nonsense codon of exon 14 reduces lysyl hydroxylase mRNA and leads to aberrant RNA splicing in a patient with Ehlers-Danlos syndrome type VI (2000) Mutat. Res., 432, pp. 33-37
  • Yamada, T., Novel mutations of the FANCG gene causing alternative splicing in Japanese Fanconi anemia (2000) J. Hum. Genet., 45, pp. 159-166
  • D'Souza, I., Missense and silent tau gene mutations cause frontotemporal dementia with parkinsonism-chromosome 17 type, by affecting multiple alternative RNA splicing regulatory elements (1999) Proc. Natl. Acad. Sci. U. S. A, 96, pp. 5598-5603
  • Stanford, P.M., Progressive supranuclear palsy pathology caused by a novel silent mutation in exon 10 of the tau gene: Expansion of the disease phenotype caused by tau gene mutations (2000) Brain, 123, pp. 880-893
  • De Meirleir, L., Aberrant splicing of exon 6 in the pyruvate dehydrogenase-E1 alpha mRNA linked to a silent mutation in a large family with Leigh's encephalomyelopathy (1994) Pediatr. Res., 36, pp. 707-712
  • Liu, W., Silent mutation induces exon skipping of fibrillin-1 gene in Marfan syndrome (1997) Nat. Genet., 16, pp. 328-329
  • Hasegawa, Y., Single exon mutation in arylsulfatase A gene has two effects: Loss of enzyme activity and aberrant splicing (1994) Hum. Genet., 93, pp. 415-420
  • Ars, E., Mutations affecting mRNA splicing are the most common molecular defects in patients with neurofibromatosis type 1 (2000) Hum. Mol. Genet., 9, pp. 237-247
  • Matsuura, T., Identification of two new aberrant splicings in the ornithine carbamoyltransferase (OCT) gene in two patients with early and late onset OCT deficiency (1995) J. Inherit. Metab. Dis., 18, pp. 273-282
  • Mendez, M., Familial porphyria cutanea tarda: Characterization of seven novel uroporphyrinogen decarboxylase mutations and frequency of common hemochromatosis alleles (1998) Am. J. Hum. Genet., 63, pp. 1363-1375
  • Wakamatsu, N., A novel exon mutation in the human β-hexosaminidase beta subunit gene affects 3′ splice site selection (1992) J. Biol. Chem., 267, pp. 2406-2413
  • Santisteban, I., Three new adenosine deaminase mutations that define a splicing enhancer and cause severe and partial phenotypes: Implications for evolution of a CpG hotspot and expression of a transduced ADA cDNA (1995) Hum. Mol. Genet., 4, pp. 2081-2087
  • Sossi, V., Premature termination mutations in exon 3 of the SMN1 gene are associated with exon skipping and a relatively mild SMA phenotype (2001) Eur. J. Hum. Genet., 9, pp. 113-120
  • Lorson, C.L., A single nucleotide in the SMN gene regulates splicing and is responsible for spinal muscular atrophy (1999) Proc. Natl. Acad. Sci. U. S. A., 96, pp. 6307-6311
  • Ploos van Amstel, J.K., Hereditary tyrosinemia type 1: Novel missense, nonsense and splice consensus mutations in the human fumarylacetoacetate hydrolase gene; variability of the genotype-phenotype relationship (1996) Hum. Genet., 97, pp. 51-59
  • Dreumont, N., A missense mutation (Q279R) in the fumarylacetoacetate hydrolase gene, responsible for hereditary tyrosinemia, acts as a splicing mutation (2001) BMC Genet., 2, p. 9

Citas:

---------- APA ----------
Cáceres, J.F. & Kornblihtt, A.R. (2002) . Alternative splicing: Multiple control mechanisms and involvement in human disease. Trends in Genetics, 18(4), 186-193.
http://dx.doi.org/10.1016/S0168-9525(01)02626-9
---------- CHICAGO ----------
Cáceres, J.F., Kornblihtt, A.R. "Alternative splicing: Multiple control mechanisms and involvement in human disease" . Trends in Genetics 18, no. 4 (2002) : 186-193.
http://dx.doi.org/10.1016/S0168-9525(01)02626-9
---------- MLA ----------
Cáceres, J.F., Kornblihtt, A.R. "Alternative splicing: Multiple control mechanisms and involvement in human disease" . Trends in Genetics, vol. 18, no. 4, 2002, pp. 186-193.
http://dx.doi.org/10.1016/S0168-9525(01)02626-9
---------- VANCOUVER ----------
Cáceres, J.F., Kornblihtt, A.R. Alternative splicing: Multiple control mechanisms and involvement in human disease. Trends Genet. 2002;18(4):186-193.
http://dx.doi.org/10.1016/S0168-9525(01)02626-9