RESUMO

Serine/arginine-rich (SR) proteins are important regulators of mRNA splicing. Several postsplicing activities have been described for a subset of shuttling SR proteins, including regulation of mRNA export and translation. Using the fibronectin gene to study the links between signal-transduction pathways and SR protein activity, we show that growth factors not only modify the alternative splicing pattern of the fibronectin gene but also alter translation of reporter messenger RNAs in an SR protein-dependent fashion, providing two coregulated levels of isoform-specific amplification. These effects are inhibited by specific small interfering RNAs against SR proteins and are mediated by the AKT kinase, which elicits opposite effects to those evoked by overexpressing SR protein kinases Clk and SRPK. These results show how SR protein activity is modified in response to extracellular stimulation, leading to a concerted regulation of splicing and translation.

Assuntos

Proteínas Nucleares/metabolismo , Fosfoproteínas/metabolismo , Biossíntese de Proteínas/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Splicing de RNA , Sequência de Aminoácidos , Animais , Núcleo Celular/química , Núcleo Celular/metabolismo , Citoplasma/química , Citoplasma/metabolismo , Fibronectinas/genética , Substâncias de Crescimento/metabolismo , Humanos , Dados de Sequência Molecular , Proteínas Nucleares/análise , Proteínas Nucleares/genética , Fosfatidilinositol 3-Quinases/metabolismo , Fosfoproteínas/análise , Fosfoproteínas/genética , Biossíntese de Proteínas/efeitos dos fármacos , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/farmacologia , Proteínas de Ligação a RNA , Fatores de Processamento de Serina-Arginina , Transdução de Sinais