Activity-dependent regulation of alternative splicing patterns in the rat brain

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-2(179) 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 Rot 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.