Epithelial-to-mesenchymal transition (EMT) and its reversal (MET) are crucial cell plasticity programs that act during development and tumor metastasis. We have previously shown that the splicing factor and proto-oncogene SF2/ASF impacts EMT/MET through production of a constitutively active splice variant of the Ron proto-oncogene. Using an in vitro model, we now show that SF2/ASF is also regulated during EMT/MET by alternative splicing associated with the nonsense-mediated mRNA decay pathway (AS-NMD). Overexpression and small interfering RNA experiments implicate the splicing regulator Sam68 in AS-NMD of SF2/ASF transcripts and in the choice between EMT/MET programs. Moreover, Sam68 modulation of SF2/ASF splicing appears to be controlled by epithelial cell-derived soluble factors that act through the ERK1/2 signaling pathway to regulate Sam68 phosphorylation. Collectively, our results reveal a hierarchy of splicing factors that integrate splicing decisions into EMT/MET programs in response to extracellular stimuli.

Valacca, C., Bonomi, S., Buratti, E., Pedrotti, S., Baralle, F., Sette, C., et al. (2010). Sam68 regulates EMT through alternative splicing-activated nonsense-mediated mRNA decay of the SF2/ASF proto-oncogene. THE JOURNAL OF CELL BIOLOGY, 191(1), 87-99 [10.1083/jcb.201001073].

Sam68 regulates EMT through alternative splicing-activated nonsense-mediated mRNA decay of the SF2/ASF proto-oncogene

SETTE, CLAUDIO;
2010-10-04

Abstract

Epithelial-to-mesenchymal transition (EMT) and its reversal (MET) are crucial cell plasticity programs that act during development and tumor metastasis. We have previously shown that the splicing factor and proto-oncogene SF2/ASF impacts EMT/MET through production of a constitutively active splice variant of the Ron proto-oncogene. Using an in vitro model, we now show that SF2/ASF is also regulated during EMT/MET by alternative splicing associated with the nonsense-mediated mRNA decay pathway (AS-NMD). Overexpression and small interfering RNA experiments implicate the splicing regulator Sam68 in AS-NMD of SF2/ASF transcripts and in the choice between EMT/MET programs. Moreover, Sam68 modulation of SF2/ASF splicing appears to be controlled by epithelial cell-derived soluble factors that act through the ERK1/2 signaling pathway to regulate Sam68 phosphorylation. Collectively, our results reveal a hierarchy of splicing factors that integrate splicing decisions into EMT/MET programs in response to extracellular stimuli.
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore BIO/16
English
Con Impact Factor ISI
Epithelial cells; mesoderm; extracellular signal-regulated map kinases; receptor protein-tyrosine kinases; base sequence; rna stability; dna-binding proteins; alternative splicing; humans; codon, nonsense; nuclear proteins; rna, messenger; adaptor proteins, signal transducing; cell differentiation; molecular sequence data; rna-binding proteins; 3' untranslated regions
Valacca, C., Bonomi, S., Buratti, E., Pedrotti, S., Baralle, F., Sette, C., et al. (2010). Sam68 regulates EMT through alternative splicing-activated nonsense-mediated mRNA decay of the SF2/ASF proto-oncogene. THE JOURNAL OF CELL BIOLOGY, 191(1), 87-99 [10.1083/jcb.201001073].
Valacca, C; Bonomi, S; Buratti, E; Pedrotti, S; Baralle, F; Sette, C; Ghigna, C; Biamonti, G
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/23593
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