A polar mechanism coordinates different regions of alternative splicing within a single gene
Alternative splicing plays a key role in generating protein diversity. Transfections with minigenes revealed coordination between two distant, alternatively spliced exons in the same gene. Mutations that either inhibit or stimulate inclusion of the upstream alternative exon deeply affect inclusion o...
Guardado en:
Autores principales: | , , , , , , , |
---|---|
Publicado: |
2005
|
Materias: | |
Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_10972765_v19_n3_p393_Fededa http://hdl.handle.net/20.500.12110/paper_10972765_v19_n3_p393_Fededa |
Aporte de: |
id |
paper:paper_10972765_v19_n3_p393_Fededa |
---|---|
record_format |
dspace |
spelling |
paper:paper_10972765_v19_n3_p393_Fededa2023-06-08T16:07:07Z A polar mechanism coordinates different regions of alternative splicing within a single gene Fededa, Juan Pablo Petrillo, Ezequiel Kadener, Sebastián Nogués, Guadalupe Pelisch, Federico Gastón Baralle, Francisco Ernesto Muro, Andrés Fernando Kornblihtt, Alberto Rodolfo fibronectin alternative RNA splicing article bioinformatics cis isomer gene identification human nonhuman transcription regulation Alleles Alpha-Globulins Alternative Splicing Animals Antigens, Viral, Tumor Cell Line, Tumor Cercopithecus aethiops Computational Biology COS Cells Dichlororibofuranosylbenzimidazole DNA-Binding Proteins Exons Fibroblasts Fibronectins Genes Humans Mice Mice, Knockout Models, Genetic Nuclear Proteins Promoter Regions (Genetics) Protein Isoforms RNA Polymerase II RNA Splicing RNA-Binding Proteins Transcription Factors Transfection Alternative splicing plays a key role in generating protein diversity. Transfections with minigenes revealed coordination between two distant, alternatively spliced exons in the same gene. Mutations that either inhibit or stimulate inclusion of the upstream alternative exon deeply affect inclusion of the downstream one. However, similar mutations at the downstream alternative exon have little effect on the upstream one. This polar effect is promoter specific and is enhanced by inhibition of transcriptional elongation. Consistently, cells from mutant mice with either constitutive or null inclusion of a fibronectin alternative exon revealed coordination with a second alternative splicing region, located far downstream. Using allele-specific RT-PCR, we demonstrate that this coordination occurs in cis and is also affected by transcriptional elongation rates. Bioinformatics supports the generality of these findings, indicating that 25% of human genes contain multiple alternative splicing regions and identifying several genes with nonrandom distribution of mRNA isoforms at two alternative regions. Copyright ©2005 by Elsevier Inc. Fil:Fededa, J.P. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Petrillo, E. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Kadener, S. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Nogués, G. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Pelisch, F. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Baralle, F.E. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Muro, A.F. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Kornblihtt, A.R. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2005 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_10972765_v19_n3_p393_Fededa http://hdl.handle.net/20.500.12110/paper_10972765_v19_n3_p393_Fededa |
institution |
Universidad de Buenos Aires |
institution_str |
I-28 |
repository_str |
R-134 |
collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
topic |
fibronectin alternative RNA splicing article bioinformatics cis isomer gene identification human nonhuman transcription regulation Alleles Alpha-Globulins Alternative Splicing Animals Antigens, Viral, Tumor Cell Line, Tumor Cercopithecus aethiops Computational Biology COS Cells Dichlororibofuranosylbenzimidazole DNA-Binding Proteins Exons Fibroblasts Fibronectins Genes Humans Mice Mice, Knockout Models, Genetic Nuclear Proteins Promoter Regions (Genetics) Protein Isoforms RNA Polymerase II RNA Splicing RNA-Binding Proteins Transcription Factors Transfection |
spellingShingle |
fibronectin alternative RNA splicing article bioinformatics cis isomer gene identification human nonhuman transcription regulation Alleles Alpha-Globulins Alternative Splicing Animals Antigens, Viral, Tumor Cell Line, Tumor Cercopithecus aethiops Computational Biology COS Cells Dichlororibofuranosylbenzimidazole DNA-Binding Proteins Exons Fibroblasts Fibronectins Genes Humans Mice Mice, Knockout Models, Genetic Nuclear Proteins Promoter Regions (Genetics) Protein Isoforms RNA Polymerase II RNA Splicing RNA-Binding Proteins Transcription Factors Transfection Fededa, Juan Pablo Petrillo, Ezequiel Kadener, Sebastián Nogués, Guadalupe Pelisch, Federico Gastón Baralle, Francisco Ernesto Muro, Andrés Fernando Kornblihtt, Alberto Rodolfo A polar mechanism coordinates different regions of alternative splicing within a single gene |
topic_facet |
fibronectin alternative RNA splicing article bioinformatics cis isomer gene identification human nonhuman transcription regulation Alleles Alpha-Globulins Alternative Splicing Animals Antigens, Viral, Tumor Cell Line, Tumor Cercopithecus aethiops Computational Biology COS Cells Dichlororibofuranosylbenzimidazole DNA-Binding Proteins Exons Fibroblasts Fibronectins Genes Humans Mice Mice, Knockout Models, Genetic Nuclear Proteins Promoter Regions (Genetics) Protein Isoforms RNA Polymerase II RNA Splicing RNA-Binding Proteins Transcription Factors Transfection |
description |
Alternative splicing plays a key role in generating protein diversity. Transfections with minigenes revealed coordination between two distant, alternatively spliced exons in the same gene. Mutations that either inhibit or stimulate inclusion of the upstream alternative exon deeply affect inclusion of the downstream one. However, similar mutations at the downstream alternative exon have little effect on the upstream one. This polar effect is promoter specific and is enhanced by inhibition of transcriptional elongation. Consistently, cells from mutant mice with either constitutive or null inclusion of a fibronectin alternative exon revealed coordination with a second alternative splicing region, located far downstream. Using allele-specific RT-PCR, we demonstrate that this coordination occurs in cis and is also affected by transcriptional elongation rates. Bioinformatics supports the generality of these findings, indicating that 25% of human genes contain multiple alternative splicing regions and identifying several genes with nonrandom distribution of mRNA isoforms at two alternative regions. Copyright ©2005 by Elsevier Inc. |
author |
Fededa, Juan Pablo Petrillo, Ezequiel Kadener, Sebastián Nogués, Guadalupe Pelisch, Federico Gastón Baralle, Francisco Ernesto Muro, Andrés Fernando Kornblihtt, Alberto Rodolfo |
author_facet |
Fededa, Juan Pablo Petrillo, Ezequiel Kadener, Sebastián Nogués, Guadalupe Pelisch, Federico Gastón Baralle, Francisco Ernesto Muro, Andrés Fernando Kornblihtt, Alberto Rodolfo |
author_sort |
Fededa, Juan Pablo |
title |
A polar mechanism coordinates different regions of alternative splicing within a single gene |
title_short |
A polar mechanism coordinates different regions of alternative splicing within a single gene |
title_full |
A polar mechanism coordinates different regions of alternative splicing within a single gene |
title_fullStr |
A polar mechanism coordinates different regions of alternative splicing within a single gene |
title_full_unstemmed |
A polar mechanism coordinates different regions of alternative splicing within a single gene |
title_sort |
polar mechanism coordinates different regions of alternative splicing within a single gene |
publishDate |
2005 |
url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_10972765_v19_n3_p393_Fededa http://hdl.handle.net/20.500.12110/paper_10972765_v19_n3_p393_Fededa |
work_keys_str_mv |
AT fededajuanpablo apolarmechanismcoordinatesdifferentregionsofalternativesplicingwithinasinglegene AT petrilloezequiel apolarmechanismcoordinatesdifferentregionsofalternativesplicingwithinasinglegene AT kadenersebastian apolarmechanismcoordinatesdifferentregionsofalternativesplicingwithinasinglegene AT noguesguadalupe apolarmechanismcoordinatesdifferentregionsofalternativesplicingwithinasinglegene AT pelischfedericogaston apolarmechanismcoordinatesdifferentregionsofalternativesplicingwithinasinglegene AT barallefranciscoernesto apolarmechanismcoordinatesdifferentregionsofalternativesplicingwithinasinglegene AT muroandresfernando apolarmechanismcoordinatesdifferentregionsofalternativesplicingwithinasinglegene AT kornblihttalbertorodolfo apolarmechanismcoordinatesdifferentregionsofalternativesplicingwithinasinglegene AT fededajuanpablo polarmechanismcoordinatesdifferentregionsofalternativesplicingwithinasinglegene AT petrilloezequiel polarmechanismcoordinatesdifferentregionsofalternativesplicingwithinasinglegene AT kadenersebastian polarmechanismcoordinatesdifferentregionsofalternativesplicingwithinasinglegene AT noguesguadalupe polarmechanismcoordinatesdifferentregionsofalternativesplicingwithinasinglegene AT pelischfedericogaston polarmechanismcoordinatesdifferentregionsofalternativesplicingwithinasinglegene AT barallefranciscoernesto polarmechanismcoordinatesdifferentregionsofalternativesplicingwithinasinglegene AT muroandresfernando polarmechanismcoordinatesdifferentregionsofalternativesplicingwithinasinglegene AT kornblihttalbertorodolfo polarmechanismcoordinatesdifferentregionsofalternativesplicingwithinasinglegene |
_version_ |
1768544789565800448 |