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Abstract:

Differential splicing from the bcl-X gene generates several isoforms with opposite effects on the apoptotic response. To explore the mechanism controlling the balance between the various isoforms, we have characterized the 5′ region of the mouse bcl-X gene. We identified three new promoters in addition to the two previously described (Grillot, D. A., M., G.-G., Ekhterae, D., Duan, L., Inohara, N., Ohta, S., Seldin, M. F., and Núñez, G. (1997) J. Immunol. 158, 4750-4757). These five promoters (P1-P5) would give rise to at least five mRNAs with different 5′-untranslated region, all sharing the same translation initiation site. Except for the product of the most proximal promoter (P1), the other mRNAs are generated by alternative splicing of noncoding exons to a common acceptor site located in the first translated exon. Reverse transcriptase-polymerase chain reaction, primer extension, and RNase protection assays demonstrate a tissue-specific pattern of promoter usage. P1 and P2 are active in all tissues analyzed, whereas the other three promoter show tissue-specific activities. P3 is active in spleen, liver, and kidney, P4 is active in uterus and spleen, and P5 is active in spleen, liver, brain, and thymus. We present evidence suggesting that promoter selection influences the outcome of the splice process. Transcripts from P1 generate mainly the mRNA for the long isoform Bcl-XL, whereas transcripts from P2 generate mRNAs for the isoforms Bcl-XL, Bcl-XS, and Bcl-Xγ and transcripts from P3 yield mainly mRNAs for the isoform Bcl-Xγ. Our results suggest a key role of promoter choice in determining alternative splicing and, thus, the balance of Bcl-X isoforms.

Registro:

Documento: Artículo
Título:Promoter Choice Influences Alternative Splicing and Determines the Balance of Isoforms Expressed from the Mouse bcl-X Gene
Autor:Pecci, A.; Viegas, L.R.; Barañao, J.L.; Beato, M.
Filiación:Inst. Mol. Biol. Tum. Forsch. (IMT), Marburg 35033, Germany
Departamento de Quimica Biologica, Inst. Biologia Med. Exp. (IByME), Universidad de Buenos Aires, Buenos Aires 1428, Argentina
Palabras clave:Brain; Genes; Genetic engineering; RNA; Tissue; Isoforms; Biochemistry; messenger RNA; protein bcl x; protein bcl x gamma; protein bcl xl; protein bcl xs; ribonuclease; unclassified drug; Bcl2l1 protein, mouse; isoprotein; messenger RNA; protein bcl 2; protein bcl x; 5' untranslated region; alternative RNA splicing; animal tissue; apoptosis; article; brain; exon; female; gene expression; gene identification; kidney; liver; male; mouse; nonhuman; nucleotide sequence; priority journal; promoter region; reverse transcription polymerase chain reaction; ribonuclease protection assay; spleen; thymus; translation initiation; uterus; 5' untranslated region; animal; genetic transcription; genetics; metabolism; molecular genetics; polymerase chain reaction; protein synthesis; Animalia; Rodentia; 5' Untranslated Regions; Alternative Splicing; Animals; Apoptosis; Base Sequence; bcl-X Protein; Brain; Exons; Female; Liver; Male; Mice; Molecular Sequence Data; Polymerase Chain Reaction; Promoter Regions (Genetics); Protein Biosynthesis; Protein Isoforms; Proto-Oncogene Proteins c-bcl-2; RNA, Messenger; Spleen; Thymus Gland; Transcription, Genetic; Uterus
Año:2001
Volumen:276
Número:24
Página de inicio:21062
Página de fin:21069
DOI: http://dx.doi.org/10.1074/jbc.M008665200
Título revista:Journal of Biological Chemistry
Título revista abreviado:J. Biol. Chem.
ISSN:00219258
CODEN:JBCHA
CAS:protein bcl xl, 151033-38-4; ribonuclease, 59794-03-5, 9001-99-4; 5' Untranslated Regions; bcl-X Protein; Bcl2l1 protein, mouse; Protein Isoforms; Proto-Oncogene Proteins c-bcl-2; RNA, Messenger
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00219258_v276_n24_p21062_Pecci

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Citas:

---------- APA ----------
Pecci, A., Viegas, L.R., Barañao, J.L. & Beato, M. (2001) . Promoter Choice Influences Alternative Splicing and Determines the Balance of Isoforms Expressed from the Mouse bcl-X Gene. Journal of Biological Chemistry, 276(24), 21062-21069.
http://dx.doi.org/10.1074/jbc.M008665200
---------- CHICAGO ----------
Pecci, A., Viegas, L.R., Barañao, J.L., Beato, M. "Promoter Choice Influences Alternative Splicing and Determines the Balance of Isoforms Expressed from the Mouse bcl-X Gene" . Journal of Biological Chemistry 276, no. 24 (2001) : 21062-21069.
http://dx.doi.org/10.1074/jbc.M008665200
---------- MLA ----------
Pecci, A., Viegas, L.R., Barañao, J.L., Beato, M. "Promoter Choice Influences Alternative Splicing and Determines the Balance of Isoforms Expressed from the Mouse bcl-X Gene" . Journal of Biological Chemistry, vol. 276, no. 24, 2001, pp. 21062-21069.
http://dx.doi.org/10.1074/jbc.M008665200
---------- VANCOUVER ----------
Pecci, A., Viegas, L.R., Barañao, J.L., Beato, M. Promoter Choice Influences Alternative Splicing and Determines the Balance of Isoforms Expressed from the Mouse bcl-X Gene. J. Biol. Chem. 2001;276(24):21062-21069.
http://dx.doi.org/10.1074/jbc.M008665200