Tissue-specific splicing of two mutually exclusive exons of the chicken beta-tropomyosin pre-mRNA: positive and negative regulations

Autor: B. Clouet d'Orval, Edward Brody, M.E. Gallego, Yves d'Aubenton-Carafa, A. Expert-Bezançon, P. Durosay, Joëlle Marie, P Sirand-Pugnet
Přispěvatelé: Centre de Génétique Moléculaire, Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherches sur les Plantes, Université Paris-Sud - Paris 11 (UP11), Centre de génétique moléculaire (CGM), Centre National de la Recherche Scientifique (CNRS), Department of Chemistry and Biochemistry [Boulder], University of Colorado [Boulder], This workwas supported by CNRS, INSERM ('contrat externe' No 88100~.), Association Franqaise contre les Myopathies (AFM), Association pour la Recherche sur le Cancer (ARC) and Ligue Nationale contrele Cancer (LNCC)., White, Charles
Rok vydání: 1996
Předmět:
Zdroj: Biochimie
Biochimie, 1996, 78 (6), pp.457-465. ⟨10.1016/0300-9084(96)84752-3⟩
Biochimie, Elsevier, 1996, 78 (6), pp.457-465. ⟨10.1016/0300-9084(96)84752-3⟩
ISSN: 0300-9084
DOI: 10.1016/0300-9084(96)84752-3⟩
Popis: International audience; Alternative splicing of premessenger RNA (pre-mRNA) is a widespread process used in higher eucaryotes to regulate gene expression. A single primary transcript can generate multiple proteins with distinct functions in a tissue- and/or developmental-specific manner. A central question in alternative splicing concerns the selection of splice sites in different cell environments. In this review, we present our results on the alternative splicing of the chicken beta-tropomyosin gene which provides an interesting model for understanding mechanisms involved in splice site selection. The beta-tropomyosin gene contains in its central portion a pair of exons (6A and 6B) that are used mutually exclusively in a tissue and developmental stage-specific manner. Exon 6A is present in mRNA of non-muscle and smooth muscle tissues while exon 6B is only present in mRNA of skeletal muscle. Regulation of both exons is necessary to ensure specific expression of beta-tropomyosin gene in non-muscle cells. Several cis-acting elements involved in the repression of exon 6B and activation of exon 6A have been identified. In addition, we show that the tissue-specific choice of exon 6A is mediated through interaction with a specific class of splicing factors, the SR proteins. In the last part of this review we will focus on possible mechanisms needed to switch to exon 6B selection in skeletal muscle tissue. We propose that tissue-specific choice of exon 6B involves down regulation of exon 6A and activation of exon 6B. A G-rich enhancer sequence downstream of exon 6B has been defined that is needed for efficient recognition of the exon 6B 5' splice site. Moreover, we suggest that alteration of the ratio between proteins of the SR family contributes to tissue-specific splice site selection.
Databáze: OpenAIRE
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