Defects in the regulation of alternative splicing have strong relevance in the onset and progression of several types of human cancer. Modulation of alternative splicing allows cancer cells to adapt to hostile environments through production of specific mRNA variants. In particular, genotoxic stress exerted by chemotherapeutic drugs or irradiation strongly affects splicing of many genes. A key role in this aberrant regulation is played by the unbalanced expression of several splicing factors in cancer cells. Among them, the RNA-binding protein Sam68, which is overexpressed in various tumors, was shown to accumulate in nuclear foci of active transcription, together with other splicing regulators, and to affect splicing of target mRNAs in response to genotoxic stress. We suggest that subcellular redistribution of splicing factors is guided by changes in chromatin conformation elicited by DNA-damaging drugs. This event might represent an escape mechanism used by cancer cells to survive to genotoxic insults through expression of pro-survival, cancer-specific gene products.

Busà, R., Sette, C. (2010). An emerging role for nuclear RNA-mediated responses to genotoxic stress. RNA BIOLOGY, 7(4), 390-396 [10.4161/rna.7.4.12466].

An emerging role for nuclear RNA-mediated responses to genotoxic stress

SETTE, CLAUDIO
2010

Abstract

Defects in the regulation of alternative splicing have strong relevance in the onset and progression of several types of human cancer. Modulation of alternative splicing allows cancer cells to adapt to hostile environments through production of specific mRNA variants. In particular, genotoxic stress exerted by chemotherapeutic drugs or irradiation strongly affects splicing of many genes. A key role in this aberrant regulation is played by the unbalanced expression of several splicing factors in cancer cells. Among them, the RNA-binding protein Sam68, which is overexpressed in various tumors, was shown to accumulate in nuclear foci of active transcription, together with other splicing regulators, and to affect splicing of target mRNAs in response to genotoxic stress. We suggest that subcellular redistribution of splicing factors is guided by changes in chromatin conformation elicited by DNA-damaging drugs. This event might represent an escape mechanism used by cancer cells to survive to genotoxic insults through expression of pro-survival, cancer-specific gene products.
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore BIO/16
English
Con Impact Factor ISI
RNA, nuclear; dna damage; gene expression regulation, neoplastic; adaptor proteins, signal transducing; neoplasms; rna-binding proteins; dna-binding proteins; humans
Busà, R., Sette, C. (2010). An emerging role for nuclear RNA-mediated responses to genotoxic stress. RNA BIOLOGY, 7(4), 390-396 [10.4161/rna.7.4.12466].
Busà, R; Sette, C
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/23600
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