DNA Damage Regulates Alternative Splicing through Inhibition of RNA Polymerase II Elongation

DNA damage induces apoptosis and many apoptotic genes are regulated via alternative splicing (AS), but little is known about the control mechanisms. Here we show that ultraviolet irradiation (UV) affects cotranscriptional AS in a p53-independent way, through the hyperphosphorylation of RNA polymeras...

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Autores principales:	Muñoz, M.J., Santangelo, M.S.P., Paronetto, M.P., de la Mata, M., Pelisch, F., Boireau, S., Glover-Cutter, K., Ben-Dov, C., Blaustein, M., Lozano, J.J., Bird, G., Bentley, D., Bertrand, E., Kornblihtt, A.R.
Formato:	JOUR
Materias:	CELLBIO DNA SIGNALING protein p53 RNA polymerase II apoptosis article controlled study DNA damage enzyme inhibition enzyme phosphorylation gene expression genetic transcription human human cell microarray analysis priority journal RNA splicing ultraviolet irradiation Alternative Splicing Apoptosis Cell Line, Tumor Dichlororibofuranosylbenzimidazole DNA Damage Fibronectins Fluorescence Recovery After Photobleaching Humans Mutation Oligonucleotide Array Sequence Analysis Phosphorylation RNA Polymerase II Transcription, Genetic Ultraviolet Rays
Acceso en línea:	http://hdl.handle.net/20.500.12110/paper_00928674_v137_n4_p708_Munoz
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	todo:paper_00928674_v137_n4_p708_Munoz
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spelling	todo:paper_00928674_v137_n4_p708_Munoz2023-10-03T14:55:21Z DNA Damage Regulates Alternative Splicing through Inhibition of RNA Polymerase II Elongation Muñoz, M.J. Santangelo, M.S.P. Paronetto, M.P. de la Mata, M. Pelisch, F. Boireau, S. Glover-Cutter, K. Ben-Dov, C. Blaustein, M. Lozano, J.J. Bird, G. Bentley, D. Bertrand, E. Kornblihtt, A.R. CELLBIO DNA SIGNALING DNA protein p53 RNA polymerase II apoptosis article controlled study DNA damage enzyme inhibition enzyme phosphorylation gene expression genetic transcription human human cell microarray analysis priority journal RNA splicing ultraviolet irradiation Alternative Splicing Apoptosis Cell Line, Tumor Dichlororibofuranosylbenzimidazole DNA Damage Fibronectins Fluorescence Recovery After Photobleaching Humans Mutation Oligonucleotide Array Sequence Analysis Phosphorylation RNA Polymerase II Transcription, Genetic Ultraviolet Rays DNA damage induces apoptosis and many apoptotic genes are regulated via alternative splicing (AS), but little is known about the control mechanisms. Here we show that ultraviolet irradiation (UV) affects cotranscriptional AS in a p53-independent way, through the hyperphosphorylation of RNA polymerase II carboxy-terminal domain (CTD) and a subsequent inhibition of transcriptional elongation, estimated in vivo and in real time. Phosphomimetic CTD mutants not only display lower elongation but also duplicate the UV effect on AS. Consistently, nonphosphorylatable mutants prevent the UV effect. Apoptosis promoted by UV in cells lacking p53 is prevented when the change in AS of the apoptotic gene bcl-x is reverted, confirming the relevance of this mechanism. Splicing-sensitive microarrays revealed a significant overlap of the subsets of genes that have changed AS with UV and those that have reduced expression, suggesting that transcriptional coupling to AS is a key feature of the DNA-damage response. © 2009 Elsevier Inc. All rights reserved. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_00928674_v137_n4_p708_Munoz
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	CELLBIO DNA SIGNALING DNA protein p53 RNA polymerase II apoptosis article controlled study DNA damage enzyme inhibition enzyme phosphorylation gene expression genetic transcription human human cell microarray analysis priority journal RNA splicing ultraviolet irradiation Alternative Splicing Apoptosis Cell Line, Tumor Dichlororibofuranosylbenzimidazole DNA Damage Fibronectins Fluorescence Recovery After Photobleaching Humans Mutation Oligonucleotide Array Sequence Analysis Phosphorylation RNA Polymerase II Transcription, Genetic Ultraviolet Rays
spellingShingle	CELLBIO DNA SIGNALING DNA protein p53 RNA polymerase II apoptosis article controlled study DNA damage enzyme inhibition enzyme phosphorylation gene expression genetic transcription human human cell microarray analysis priority journal RNA splicing ultraviolet irradiation Alternative Splicing Apoptosis Cell Line, Tumor Dichlororibofuranosylbenzimidazole DNA Damage Fibronectins Fluorescence Recovery After Photobleaching Humans Mutation Oligonucleotide Array Sequence Analysis Phosphorylation RNA Polymerase II Transcription, Genetic Ultraviolet Rays Muñoz, M.J. Santangelo, M.S.P. Paronetto, M.P. de la Mata, M. Pelisch, F. Boireau, S. Glover-Cutter, K. Ben-Dov, C. Blaustein, M. Lozano, J.J. Bird, G. Bentley, D. Bertrand, E. Kornblihtt, A.R. DNA Damage Regulates Alternative Splicing through Inhibition of RNA Polymerase II Elongation
topic_facet	CELLBIO DNA SIGNALING DNA protein p53 RNA polymerase II apoptosis article controlled study DNA damage enzyme inhibition enzyme phosphorylation gene expression genetic transcription human human cell microarray analysis priority journal RNA splicing ultraviolet irradiation Alternative Splicing Apoptosis Cell Line, Tumor Dichlororibofuranosylbenzimidazole DNA Damage Fibronectins Fluorescence Recovery After Photobleaching Humans Mutation Oligonucleotide Array Sequence Analysis Phosphorylation RNA Polymerase II Transcription, Genetic Ultraviolet Rays
description	DNA damage induces apoptosis and many apoptotic genes are regulated via alternative splicing (AS), but little is known about the control mechanisms. Here we show that ultraviolet irradiation (UV) affects cotranscriptional AS in a p53-independent way, through the hyperphosphorylation of RNA polymerase II carboxy-terminal domain (CTD) and a subsequent inhibition of transcriptional elongation, estimated in vivo and in real time. Phosphomimetic CTD mutants not only display lower elongation but also duplicate the UV effect on AS. Consistently, nonphosphorylatable mutants prevent the UV effect. Apoptosis promoted by UV in cells lacking p53 is prevented when the change in AS of the apoptotic gene bcl-x is reverted, confirming the relevance of this mechanism. Splicing-sensitive microarrays revealed a significant overlap of the subsets of genes that have changed AS with UV and those that have reduced expression, suggesting that transcriptional coupling to AS is a key feature of the DNA-damage response. © 2009 Elsevier Inc. All rights reserved.
format	JOUR
author	Muñoz, M.J. Santangelo, M.S.P. Paronetto, M.P. de la Mata, M. Pelisch, F. Boireau, S. Glover-Cutter, K. Ben-Dov, C. Blaustein, M. Lozano, J.J. Bird, G. Bentley, D. Bertrand, E. Kornblihtt, A.R.
author_facet	Muñoz, M.J. Santangelo, M.S.P. Paronetto, M.P. de la Mata, M. Pelisch, F. Boireau, S. Glover-Cutter, K. Ben-Dov, C. Blaustein, M. Lozano, J.J. Bird, G. Bentley, D. Bertrand, E. Kornblihtt, A.R.
author_sort	Muñoz, M.J.
title	DNA Damage Regulates Alternative Splicing through Inhibition of RNA Polymerase II Elongation
title_short	DNA Damage Regulates Alternative Splicing through Inhibition of RNA Polymerase II Elongation
title_full	DNA Damage Regulates Alternative Splicing through Inhibition of RNA Polymerase II Elongation
title_fullStr	DNA Damage Regulates Alternative Splicing through Inhibition of RNA Polymerase II Elongation
title_full_unstemmed	DNA Damage Regulates Alternative Splicing through Inhibition of RNA Polymerase II Elongation
title_sort	dna damage regulates alternative splicing through inhibition of rna polymerase ii elongation
url	http://hdl.handle.net/20.500.12110/paper_00928674_v137_n4_p708_Munoz
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DNA Damage Regulates Alternative Splicing through Inhibition of RNA Polymerase II Elongation

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