O'Leary Debra A, Koleski Daniela, Kola Ismail, Hertzog Paul J, Ristevski Sika
Centre for Functional Genomics and Human Disease, Monash Institute of Reproduction and Development, Monash Medical Centre, Monash University, Clayton 246 Clayton Road, Clayton, Victoria 3168, Australia.
Gene. 2005 Jan 3;344:79-92. doi: 10.1016/j.gene.2004.09.031. Epub 2004 Nov 23.
The erythroblast transformation specific (ETS) transcription factor GA-binding protein (Gabp) is widely expressed and acts on a diverse range of target genes, including nuclear-encoded mitochondrial proteins and neuromuscular-specific genes. The GABPalpha subunit contains an ETS DNA binding domain and the beta subunit contains a nuclear localization signal (NLS) and transactivation domain. Here, we show coincident expression of Gabpalpha and beta1 throughout mouse embryogenesis, consistent with the gene products functioning in a complex. We have also identified 2 alternatively spliced, tissue-specific exons 1 (5' untranslated regions) of mouse Gabpalpha and 4 alternative 3' polyadenylation signals that, in combination, result in 12 transcripts for Gabpalpha. These alternative transcripts are suggested to have altered stability, subcellular localization and/or translation efficiency. Further, we identified nine differentially expressed splice variants of mouse Gabpbeta1 that encode beta protein forms lacking functional domains, suggesting a dominant negative function. Together, alternative transcripts of Gabpalpha and beta1 provide a mechanism for tissue-specific regulation of Gabp activity.
成红细胞转化特异性(ETS)转录因子GA结合蛋白(Gabp)广泛表达,并作用于多种靶基因,包括核编码的线粒体蛋白和神经肌肉特异性基因。GABPα亚基包含一个ETS DNA结合结构域,β亚基包含一个核定位信号(NLS)和反式激活结构域。在此,我们展示了Gabpα和β1在整个小鼠胚胎发育过程中的共表达,这与基因产物在一个复合物中发挥功能一致。我们还鉴定出小鼠Gabpα的2个可变剪接的组织特异性外显子1(5'非翻译区)和4个可变的3'聚腺苷酸化信号,它们共同产生12种Gabpα转录本。这些可变转录本被认为具有改变的稳定性、亚细胞定位和/或翻译效率。此外,我们鉴定出小鼠Gabpβ1的9种差异表达的剪接变体,它们编码缺乏功能结构域的β蛋白形式,提示存在显性负性功能。总之,Gabpα和β1的可变转录本为Gabp活性的组织特异性调节提供了一种机制。