Daoud R, Da Penha Berzaghi M, Siedler F, Hübener M, Stamm S
Max-Planck Institute of Neurobiology, D-82152 Martinsried, Germany.
Eur J Neurosci. 1999 Mar;11(3):788-802. doi: 10.1046/j.1460-9568.1999.00486.x.
Alternative splicing plays an important role in the expression of genetic information. Among the best understood alternative splicing factors are transformer and transformer-2, which regulate sexual differentiation in Drosophila. Like the Drosophila genes, the recently identified mammalian homologues are subject to alternative splicing. Using an antibody directed against the major human transformer-2 beta isoform, we show that it has a widespread expression in the rat brain. Pilocarpine-induced neuronal activity changes the alternative splicing pattern of the human transformer-2-beta gene in the brain. After neuronal stimulation, a variant bearing high similarity to a male-specific Drosophila tra-2179 isoform is switched off in the hippocampus and is detectable in the cortex. In addition, the ratio of another short RNA isoform (htra2-beta2) to htra2-beta1 is changed. Htra2-beta2 is not translated into protein, and probably helps to regulate the relative amounts of htra2-beta1 to beta3. We also observe activity-dependent changes in alternative splicing of the clathrin light chain B, c-src and NMDAR1 genes, indicating that the coordinated change of alternative splicing patterns might contribute to molecular plasticity in the brain.
可变剪接在遗传信息的表达中起着重要作用。在已被深入了解的可变剪接因子中，有transformer和transformer-2，它们调控果蝇的性别分化。与果蝇基因一样，最近鉴定出的哺乳动物同源物也会发生可变剪接。我们使用针对主要的人类transformer-2β异构体的抗体，发现它在大鼠脑中广泛表达。毛果芸香碱诱导的神经元活动改变了脑中人类transformer-2-β基因的可变剪接模式。神经元刺激后，一种与雄性特异性果蝇tra-2179异构体高度相似的变体在海马体中被关闭，而在皮质中可检测到。此外，另一种短RNA异构体（htra2-β2）与htra2-β1的比例发生了变化。htra2-β2不会被翻译成蛋白质，可能有助于调节htra2-β1与β3的相对含量。我们还观察到网格蛋白轻链B、c-src和NMDAR1基因可变剪接的活性依赖性变化，这表明可变剪接模式的协同变化可能有助于大脑中的分子可塑性。
