Regulation of fosB and DeltafosB mRNA expression: in vivo and in vitro studies.
Regulation of fosB and DeltafosB mRNA expression: in vivo and in vitro studies.
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DOI：
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发表时间：
2007
期刊：
影响因子：
2.9
通讯作者：
I. Alibhai;T. Green;J. Potashkin;E. Nestler
中科院分区：
文献类型：
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作者：
I. Alibhai;T. Green;J. Potashkin;E. Nestler
转录因子DeltaFosB是FosB的截短剪接异构体，在几种类型的慢性刺激后在脑中积累。这种积累被认为是由DeltaFosB与所有其他Fos家族蛋白相比的独特稳定性介导的。本研究的目的是确定两种fosB亚型的相对表达是否也在mRNA水平上受到调节，从而进一步促进慢性刺激后DeltaFosB的选择性积累。首先，与蛋白质不同，在体外培养细胞和体内脑中，DeltafosB mRNA的半衰期仅略长于全长fosB mRNA的半衰期。此外，类似于c-fos，fosB亚型诱导大量的急性管理安非他明或应力后，在纹状体，部分脱敏后慢性曝光。令人惊讶的是，DeltafosB与fosB mRNA的相对比率在急性刺激后而不是慢性刺激后增加最显著。最后，在培养的细胞中，调节RNA剪接的多聚嘧啶束结合蛋白（PTB 1）的过表达降低了DeltafosB相对于fosB mRNA的表达。总之，这些研究结果表明，剪接fosB前mRNA的调节量的未剪接的转录本提供给剪接机器。这些数据提供了关于DeltaFosB mRNA生成的基本信息，并表明DeltaFosB蛋白在慢性刺激下的选择性积累不涉及其通过RNA剪接的优先生成。
The transcription factor DeltaFosB, a truncated splice isoform of FosB, accumulates in brain after several types of chronic stimulation. This accumulation is thought to be mediated by the unique stability of DeltaFosB compared to all other Fos family proteins. The goal of the present study was to determine if the relative expression of the two fosB isoforms is also regulated at the mRNA level, thereby further contributing to the selective accumulation of DeltaFosB after chronic stimulation. First, unlike the protein, the half-life of DeltafosB mRNA is only slightly longer than that of full-length fosB mRNA both in cultured cells in vitro and in the brain in vivo. Additionally, similar to c-fos, both fosB isoforms are induced abundantly in striatum after acute administration of amphetamine or stress, and partially desensitize after chronic exposures. Surprisingly, the relative ratio of DeltafosB to fosB mRNA increases most significantly after acute, not chronic, stimulation. Finally, overexpression of polypyrimidine tract binding protein (PTB1), which regulates RNA splicing, in cultured cells decreases the relative expression of DeltafosB compared to fosB mRNA. Together, these findings suggest that splicing of fosB pre-mRNA is regulated by the quantity of unspliced transcript available to the splicing machinery. These data provide fundamental information concerning the generation of DeltafosB mRNA, and indicate that the selective accumulation of DeltaFosB protein with chronic stimulation does not involve its preferential generation by RNA splicing.