An alternative splicing network links cell-cycle control to apoptosis.
Cell
; 142(4): 625-36, 2010 Aug 20.
Article
en En
| MEDLINE
| ID: mdl-20705336
ABSTRACT
Alternative splicing is a vast source of biological regulation and diversity that is misregulated in cancer and other diseases. To investigate global control of alternative splicing in human cells, we analyzed splicing of mRNAs encoding Bcl2 family apoptosis factors in a genome-wide siRNA screen. The screen identified many regulators of Bcl-x and Mcl1 splicing, notably an extensive network of cell-cycle factors linked to aurora kinase A. Drugs or siRNAs that induce mitotic arrest promote proapoptotic splicing of Bcl-x, Mcl1, and caspase-9 and alter splicing of other apoptotic transcripts. This response precedes mitotic arrest, indicating coordinated upregulation of prodeath splice variants that promotes apoptosis in arrested cells. These shifts correspond to posttranslational turnover of splicing regulator ASF/SF2, which directly binds and regulates these target mRNAs and globally regulates apoptosis. Broadly, our results reveal an alternative splicing network linking cell-cycle control to apoptosis.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Proteínas Nucleares
/
Ciclo Celular
/
Regulación de la Expresión Génica
/
Apoptosis
/
Empalme Alternativo
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Cell
Año:
2010
Tipo del documento:
Article
País de afiliación:
Estados Unidos