title: Activity-dependent regulation of alternative splicing patterns in the rat brain.
abstract: 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.
authors: Max-Planck Institute of Neurobiology, D-82152 Martinsried, Germany.
authors: R
authors: R
authors: Daoud
authors: M
authors: M
authors: Da Penha Berzaghi
authors: F
authors: F
authors: Siedler
authors: M
authors: M
authors: Hübener
authors: S
authors: S
authors: Stamm
mesh_terms: D017398:Alternative Splicing / Q000502:physiology*; D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies; D001923:Brain Chemistry / Q000502:physiology*; D002540:Cerebral Cortex / Q000737:chemistry; D002966:Clathrin / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D016391:Genes, src / Q000502:physiology; D006624:Hippocampus / Q000737:chemistry; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D018721:Muscarinic Agonists / Q000494:pharmacology; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000737:chemistry / Q000502:physiology; D009687:Nuclear Proteins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D010766:Phosphorylation; D010862:Pilocarpine / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D016601:RNA-Binding Proteins; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics; D012260:Ribonucleases; D000068103:Serine-Arginine Splicing Factors
chemical_list: D000906:Antibodies; D002966:Clathrin; D018721:Muscarinic Agonists; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D010862:Pilocarpine; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D016194:Receptors, N-Methyl-D-Aspartate; D012260:Ribonucleases; D000068103:Serine-Arginine Splicing Factors; C097083:TRA2B protein, human; C490770:Tra2b protein, rat