Artículo

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" (2009) Cell. 137(4):708-720
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Abstract:

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.

Registro:

Documento: Artículo
Título:DNA Damage Regulates Alternative Splicing through Inhibition of RNA Polymerase II Elongation
Autor: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.
Filiación:Laboratorio de Fisiología y Biología Molecular, Departamento de Fisiología, Biología Molecular y Celular, IFIBYNE-CONICET, Pabellón 2, (C1428EHA) Buenos Aires, Argentina
Department of Biochemistry and Molecular Genetics, University of Colorado Denver School of Medicine, MS8101, Aurora, CO 80045, United States
Centre de Regulació Genòmica, Dr. Aiguader 88, 08003 Barcelona, Spain
IGMM-CNRS UMR 5535, 1919, Route de Mende, 34293 Montpellier, France
Palabras clave: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
Año:2009
Volumen:137
Número:4
Página de inicio:708
Página de fin:720
DOI: http://dx.doi.org/10.1016/j.cell.2009.03.010
Título revista:Cell
Título revista abreviado:Cell
ISSN:00928674
CODEN:CELLB
CAS:DNA, 9007-49-2; Dichlororibofuranosylbenzimidazole, 53-85-0; Fibronectins; RNA Polymerase II, 2.7.7.-
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00928674_v137_n4_p708_Munoz

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Citas:

---------- APA ----------
Muñoz, M.J., Santangelo, M.S.P., Paronetto, M.P., de la Mata, M., Pelisch, F., Boireau, S., Glover-Cutter, K.,..., Kornblihtt, A.R. (2009) . DNA Damage Regulates Alternative Splicing through Inhibition of RNA Polymerase II Elongation. Cell, 137(4), 708-720.
http://dx.doi.org/10.1016/j.cell.2009.03.010
---------- CHICAGO ----------
Muñoz, M.J., Santangelo, M.S.P., Paronetto, M.P., de la Mata, M., Pelisch, F., Boireau, S., et al. "DNA Damage Regulates Alternative Splicing through Inhibition of RNA Polymerase II Elongation" . Cell 137, no. 4 (2009) : 708-720.
http://dx.doi.org/10.1016/j.cell.2009.03.010
---------- MLA ----------
Muñoz, M.J., Santangelo, M.S.P., Paronetto, M.P., de la Mata, M., Pelisch, F., Boireau, S., et al. "DNA Damage Regulates Alternative Splicing through Inhibition of RNA Polymerase II Elongation" . Cell, vol. 137, no. 4, 2009, pp. 708-720.
http://dx.doi.org/10.1016/j.cell.2009.03.010
---------- VANCOUVER ----------
Muñoz, M.J., Santangelo, M.S.P., Paronetto, M.P., de la Mata, M., Pelisch, F., Boireau, S., et al. DNA Damage Regulates Alternative Splicing through Inhibition of RNA Polymerase II Elongation. Cell. 2009;137(4):708-720.
http://dx.doi.org/10.1016/j.cell.2009.03.010