Blaustein Matías, Pelisch Federico, Tanos Tamara, Muñoz Manuel J, Wengier Diego, Quadrana Leandro, Sanford Jeremy R, Muschietti Jorge P, Kornblihtt Alberto R, Cáceres Javier F, Coso Omar A, Srebrow Anabella
Instituto de Fisiología, Biología Molecular y Neurociencias, Consejo Nacional de Investigaciones Científicas y Técnicas, Departamento de Fisiología, Biología Molecular y Celular, Universidad de Buenos Aires, Ciudad Universitaria, Argentina.
Nat Struct Mol Biol. 2005 Dec;12(12):1037-44. doi: 10.1038/nsmb1020. Epub 2005 Nov 20.
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.
富含丝氨酸/精氨酸（SR）的蛋白质是mRNA剪接的重要调节因子。对于一部分穿梭SR蛋白，已经描述了几种剪接后活动，包括对mRNA输出和翻译的调节。利用纤连蛋白基因研究信号转导途径与SR蛋白活性之间的联系，我们发现生长因子不仅会改变纤连蛋白基因的可变剪接模式，还会以SR蛋白依赖的方式改变报告信使RNA的翻译，提供两种共同调节的异构体特异性扩增水平。这些效应被针对SR蛋白的特异性小干扰RNA所抑制，并由AKT激酶介导，AKT激酶产生的效应与过表达SR蛋白激酶Clk和SRPK所引起的效应相反。这些结果表明了SR蛋白活性如何响应细胞外刺激而被修饰，从而导致剪接和翻译的协同调节。
