Splicing switch of an epigenetic regulator by RNA helicases promotes tumor-cell invasiveness.
Nat Struct Mol Biol
; 19(11): 1139-46, 2012 Nov.
Article
en En
| MEDLINE
| ID: mdl-23022728
ABSTRACT
Both epigenetic and splicing regulation contribute to tumor progression, but the potential links between these two levels of gene-expression regulation in pathogenesis are not well understood. Here, we report that the mouse and human RNA helicases Ddx17 and Ddx5 contribute to tumor-cell invasiveness by regulating alternative splicing of several DNA- and chromatin-binding factors, including the macroH2A1 histone. We show that macroH2A1 splicing isoforms differentially regulate the transcription of a set of genes involved in redox metabolism. In particular, the SOD3 gene that encodes the extracellular superoxide dismutase and plays a part in cell migration is regulated in an opposite manner by macroH2A1 splicing isoforms. These findings reveal a new regulatory pathway in which splicing factors control the expression of histone variant isoforms that in turn drive a transcription program to switch tumor cells to an invasive phenotype.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Histonas
/
Regulación Neoplásica de la Expresión Génica
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Empalme Alternativo
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Epigénesis Genética
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ARN Helicasas DEAD-box
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Invasividad Neoplásica
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Nat Struct Mol Biol
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2012
Tipo del documento:
Article