A polar mechanism coordinates different regions of alternative splicing within a single gene

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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
Publicado:	2005
Materias:	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
Acceso en línea:	http://hdl.handle.net/20.500.12110/paper_10972765_v19_n3_p393_Fededa http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=artiaex&d=paper_10972765_v19_n3_p393_Fededa_oai
Aporte de:	Repositorio Digital de la Universidad de Buenos Aires (UBA) de Universidad de Buenos Aires

id	I28-R145-paper_10972765_v19_n3_p393_Fededa_oai
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spelling	I28-R145-paper_10972765_v19_n3_p393_Fededa_oai2020-10-19 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. 2005 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. application/pdf http://hdl.handle.net/20.500.12110/paper_10972765_v19_n3_p393_Fededa info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar Mol. Cell 2005;19(3):393-404 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 A polar mechanism coordinates different regions of alternative splicing within a single gene info:eu-repo/semantics/article info:ar-repo/semantics/artículo info:eu-repo/semantics/publishedVersion http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=artiaex&d=paper_10972765_v19_n3_p393_Fededa_oai
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-145
collection	Repositorio Digital de la Universidad de Buenos Aires (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, 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 http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=artiaex&d=paper_10972765_v19_n3_p393_Fededa_oai
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A polar mechanism coordinates different regions of alternative splicing within a single gene

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