| First Author | Dardenne E | Year | 2012 |
| Journal | Nat Struct Mol Biol | Volume | 19 |
| Issue | 11 | Pages | 1139-46 |
| PubMed ID | 23022728 | Mgi Jnum | J:238450 |
| Mgi Id | MGI:5819339 | Doi | 10.1038/nsmb.2390 |
| Citation | Dardenne E, et al. (2012) Splicing switch of an epigenetic regulator by RNA helicases promotes tumor-cell invasiveness. Nat Struct Mol Biol 19(11):1139-46 |
| abstractText | 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. |
