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, J.P., Petrillo, E., Gelfand, M.S., Neverov, A.D., Kadener, S., Nogués, G., Pelisch, F., Baralle, F.E., Muro, A.F., Kornblihtt, A.R.
Formato: Artículo publishedVersion
Lenguaje:Inglés
Publicado: 2005
Materias:
Acceso en línea:http://hdl.handle.net/20.500.12110/paper_10972765_v19_n3_p393_Fededa
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spelling paperaa:paper_10972765_v19_n3_p393_Fededa2023-06-12T16:49:40Z A polar mechanism coordinates different regions of alternative splicing within a single gene Mol. Cell 2005;19(3):393-404 Fededa, J.P. Petrillo, E. Gelfand, M.S. Neverov, A.D. Kadener, S. Nogués, G. Pelisch, F. Baralle, F.E. Muro, A.F. Kornblihtt, A.R. 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 info:eu-repo/semantics/article info:ar-repo/semantics/artículo info:eu-repo/semantics/publishedVersion application/pdf eng info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar 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)
language Inglés
orig_language_str_mv eng
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, J.P.
Petrillo, E.
Gelfand, M.S.
Neverov, A.D.
Kadener, S.
Nogués, G.
Pelisch, F.
Baralle, F.E.
Muro, A.F.
Kornblihtt, A.R.
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.
format Artículo
Artículo
publishedVersion
author Fededa, J.P.
Petrillo, E.
Gelfand, M.S.
Neverov, A.D.
Kadener, S.
Nogués, G.
Pelisch, F.
Baralle, F.E.
Muro, A.F.
Kornblihtt, A.R.
author_facet Fededa, J.P.
Petrillo, E.
Gelfand, M.S.
Neverov, A.D.
Kadener, S.
Nogués, G.
Pelisch, F.
Baralle, F.E.
Muro, A.F.
Kornblihtt, A.R.
author_sort Fededa, J.P.
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 http://hdl.handle.net/20.500.12110/paper_10972765_v19_n3_p393_Fededa
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