Du C, McGuffin M E, Dauwalder B, Rabinow L, Mattox W
Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha 68198, USA.
Mol Cell. 1998 Dec;2(6):741-50. doi: 10.1016/s1097-2765(00)80289-0.
Alternative mRNA splicing directed by SR proteins and the splicing regulators TRA and TRA2 is an essential feature of Drosophila sex determination. These factors are highly phosphorylated, but the role of their phosphorylation in vivo is unclear. We show that mutations in the Drosophila LAMMER kinase, Doa, alter sexual differentiation and interact synergistically with tra and tra2 mutations. Doa mutations disrupt sex-specific splicing of doublesex pre-mRNA, a key regulator of sex determination, by affecting the phosphorylation of one or more proteins in the female-specific splicing enhancer complex. Examination of pre-mRNAs regulated similarly to dsx shows that the requirement for Doa is substrate specific. These results demonstrate that a SR protein kinase plays a specific role in developmentally regulated alternative splicing.
由SR蛋白以及剪接调节因子TRA和TRA2指导的可变mRNA剪接是果蝇性别决定的一个基本特征。这些因子高度磷酸化，但其磷酸化在体内的作用尚不清楚。我们发现，果蝇LAMMER激酶Doa的突变会改变性别分化，并与tra和tra2突变产生协同作用。Doa突变通过影响雌性特异性剪接增强子复合物中一种或多种蛋白质的磷酸化，破坏了性别决定的关键调节因子双性基因前体mRNA的性别特异性剪接。对与dsx类似调控的前体mRNA的研究表明，对Doa的需求具有底物特异性。这些结果表明，一种SR蛋白激酶在发育调控的可变剪接中发挥特定作用。
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