Promoter Choice Influences Alternative Splicing and Determines the Balance of Isoforms Expressed from the Mouse bcl-X Gene
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 addit...
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todo:paper_00219258_v276_n24_p21062_Pecci2023-10-03T14:23:00Z Promoter Choice Influences Alternative Splicing and Determines the Balance of Isoforms Expressed from the Mouse bcl-X Gene Pecci, A. Viegas, L.R. Barañao, J.L. Beato, M. 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 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. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_00219258_v276_n24_p21062_Pecci |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
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 |
| spellingShingle |
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 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 |
| topic_facet |
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 |
| description |
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. |
| format |
JOUR |
| author |
Pecci, A. Viegas, L.R. Barañao, J.L. Beato, M. |
| author_facet |
Pecci, A. Viegas, L.R. Barañao, J.L. Beato, M. |
| author_sort |
Pecci, A. |
| title |
Promoter Choice Influences Alternative Splicing and Determines the Balance of Isoforms Expressed from the Mouse bcl-X Gene |
| title_short |
Promoter Choice Influences Alternative Splicing and Determines the Balance of Isoforms Expressed from the Mouse bcl-X Gene |
| title_full |
Promoter Choice Influences Alternative Splicing and Determines the Balance of Isoforms Expressed from the Mouse bcl-X Gene |
| title_fullStr |
Promoter Choice Influences Alternative Splicing and Determines the Balance of Isoforms Expressed from the Mouse bcl-X Gene |
| title_full_unstemmed |
Promoter Choice Influences Alternative Splicing and Determines the Balance of Isoforms Expressed from the Mouse bcl-X Gene |
| title_sort |
promoter choice influences alternative splicing and determines the balance of isoforms expressed from the mouse bcl-x gene |
| url |
http://hdl.handle.net/20.500.12110/paper_00219258_v276_n24_p21062_Pecci |
| work_keys_str_mv |
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