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

Roberta Busà, Claudio Sette

Research output: Contribution to journalArticlepeer-review

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 tumours, 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.

Original languageEnglish
Pages (from-to)390-396
Number of pages7
JournalRNA Biology
Volume7
Issue number4
DOIs
Publication statusPublished - Jul 2010

Keywords

  • Alternative splicing
  • Chromatin structure
  • Genotoxic stress
  • Nuclear stress granules
  • Sam68

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

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