Kirkness E F, Fraser C M
Section on Molecular Neurobiology, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, Maryland 20852.
J Biol Chem. 1993 Feb 25;268(6):4420-8.
The gene that encodes the beta 3 subunit of the gamma-aminobutyrate-Type A (GABAA) receptor is widely expressed in brain tissue and has been associated with imprinted genetic disorders. Here, the 5' regions of the human and rat genes were characterized and found to be highly conserved in both coding and non-coding sequences. A novel transcript of the human gene revealed the existence of an alternative exon 1 (exon 1a) that encodes a variant signal sequence. Relative levels of the alternative transcripts were found to vary between fetal and adult brain, and between different brain regions. Endogenous beta 3 subunit transcripts were also detected in several immortalized cell lines, including human kidney 293 cells. Transcription of exon 1 is initiated from multiple sites within a pyrimidine-rich region of the gene. This region of the human gene also exhibits strong promoter activity and binds nuclear factors at a site which overlaps the transcriptional start sites. The promoter element was shown to bind Sp1 and at least one other unidentified nuclear factor.
编码γ-氨基丁酸A型（GABAA）受体β3亚基的基因在脑组织中广泛表达，并与印记基因疾病有关。在此，对人和大鼠基因的5'区域进行了特征分析，发现其在编码和非编码序列中都高度保守。人类基因的一种新转录本揭示了一个编码可变信号序列的替代外显子1（外显子1a）的存在。发现替代转录本的相对水平在胎儿和成人脑中以及不同脑区之间有所不同。在几种永生化细胞系中也检测到了内源性β3亚基转录本，包括人肾293细胞。外显子1的转录起始于基因富含嘧啶区域内的多个位点。人类基因的这一区域还表现出很强的启动子活性，并在与转录起始位点重叠的位点结合核因子。已证明启动子元件可结合Sp1和至少一种其他未鉴定的核因子。
