Artículo
GSK-3 is an RNA polymerase II phospho-CTD kinase
Nieto Moreno, Nicolás
; Villafañez, Florencia
; Giono, Luciana Eugenia
; Cuenca, Carmen; Soria, Gastón; Muñoz, Manuel Javier
; Kornblihtt, Alberto Rodolfo
Fecha de publicación:
05/2020
Editorial:
Oxford University Press
Revista:
Nucleic Acids Research
ISSN:
1362-4962
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
We have previously found that UV-induced DNA damage causes hyperphosphorylation of the carboxy terminal domain (CTD) of RNA polymerase II (RNAPII), inhibition of transcriptional elongation and changes in alternative splicing (AS) due to kinetic coupling between transcription and splicing. In an unbiased search for protein kinases involved in the AS response to DNA damage, we have identified glycogen synthase kinase 3 (GSK-3) as an unforeseen participant. Unlike Cdk9 inhibition, GSK-3 inhibition only prevents CTD hyperphosphorylation triggered by UV but not basal phosphorylation. This effect is not due to differential degradation of the phospho-CTD isoforms and can be reproduced, at the AS level, by overexpression of a kinase-dead GSK-3 dominant negative mutant. GSK-3 inhibition abrogates both the reduction in RNAPII elongation and changes in AS elicited by UV. We show that GSK-3 phosphorylates the CTD in vitro, but preferentially when the substrate is previously phosphorylated, consistently with the requirement of a priming phosphorylation reported for GSK-3 efficacy. In line with a role for GSK-3 in the response to DNA damage, GSK-3 inhibition prevents UV-induced apoptosis. In summary, we uncover a novel role for a widely studied kinase in key steps of eukaryotic transcription and pre-mRNA processing.
Palabras clave:
RNA polymerase II
,
GSK-3
,
Transcription
,
Alternative splicing
Archivos asociados
Licencia
Identificadores
Colecciones
Articulos(IFIBYNE)
Articulos de INST.DE FISIOL., BIOL.MOLECULAR Y NEUROCIENCIAS
Articulos de INST.DE FISIOL., BIOL.MOLECULAR Y NEUROCIENCIAS
Citación
Nieto Moreno, Nicolás; Villafañez, Florencia; Giono, Luciana Eugenia; Cuenca, Carmen; Soria, Gastón; et al.; GSK-3 is an RNA polymerase II phospho-CTD kinase; Oxford University Press; Nucleic Acids Research; 48; 11; 5-2020; 6068-6080
Compartir
Altmétricas