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...

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Autores principales: Fededa, Juan Pablo, Petrillo, Ezequiel, Kadener, Sebastián, Nogués, Guadalupe, Pelisch, Federico Gastón, Baralle, Francisco Ernesto, Muro, Andrés Fernando, Kornblihtt, Alberto Rodolfo
Publicado: 2005
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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
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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
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