Koushika S P, Lisbin M J, White K
Biology Department, Brandeis University, Waltham, Massachusetts 02254, USA.
Curr Biol. 1996 Dec 1;6(12):1634-41. doi: 10.1016/s0960-9822(02)70787-2.
Tissue-specific alternative pre-mRNA splicing is a widely used mechanism for gene regulation and the generation of different protein isoforms, but relatively little is known about the factors and mechanisms that mediate this process. Tissue-specific RNA-binding proteins could mediate alternative pre-mRNA splicing. In Drosophila melanogaster, the RNA-binding protein encoded by the elav (embryonic lethal abnormal visual system) gene is a candidate for such a role. The ELAV protein is expressed exclusively in neurons, and is important for the formation and maintenance of the nervous system.
In this study, photoreceptor neurons genetically depleted of ELAV, and elav-null central nervous system neurons, were analyzed immunocytochemically for the expression of neural proteins. In both situations, the lack of ELAV corresponded with a decrease in the immunohistochemical signal of the neural-specific isoform of Neuroglian, which is generated by alternative splicing. Furthermore, when ELAV was expressed ectopically in cells that normally express only the non-neural isoform of Neuroglian, we observed the generation of the neural isoform of Neuroglian.
Drosophila ELAV promotes the generation of the neuron-specific isoform of Neuroglian by the regulation of pre-mRNA splicing. The findings reported in this paper demonstrate that ELAV is necessary, and the ectopic expression of ELAV in imaginal disc cells is sufficient, to mediate neuron-specific alternative splicing.
组织特异性可变前体mRNA剪接是一种广泛用于基因调控和产生不同蛋白质异构体的机制,但对于介导这一过程的因素和机制了解相对较少。组织特异性RNA结合蛋白可能介导可变前体mRNA剪接。在黑腹果蝇中,由elav(胚胎致死异常视觉系统)基因编码的RNA结合蛋白是担任这一角色的候选者。ELAV蛋白仅在神经元中表达,对神经系统的形成和维持很重要。
在本研究中,对基因敲除ELAV的感光神经元以及elav基因缺失的中枢神经系统神经元进行了免疫细胞化学分析,以检测神经蛋白的表达。在这两种情况下,ELAV的缺失都与通过可变剪接产生的神经特异性Neuroglian异构体的免疫组化信号减少相对应。此外,当ELAV在通常仅表达Neuroglian非神经异构体的细胞中异位表达时,我们观察到了神经特异性Neuroglian异构体的产生。
果蝇ELAV通过调控前体mRNA剪接促进Neuroglian神经元特异性异构体的产生。本文报道的研究结果表明,ELAV对于介导神经元特异性可变剪接是必要的,并且ELAV在成虫盘细胞中的异位表达足以介导该过程。