Kitanaka J, Wang X B, Kitanaka N, Hembree C M, Uhl G R
Molecular Neurobiology Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA.
DNA Seq. 2001 Dec;12(5-6):345-54. doi: 10.3109/10425170109084458.
The functional significance of heterotrimeric guanine nucleotide binding protein (G protein) for the many physiological processes including the molecular mechanisms of drug addiction have been described. In investigating the changes of mRNA expression after acute psychostimulant administration, we previously identified a cDNA encoding a G protein beta1 subunit (Gbeta1) that was increased up to four-fold in certain brain regions after administration of psychostimulants. The mouse Gbeta1 gene (the mouse genetic symbol, GNB1) was mapped to chromosome 4, but little was known of its genetic features. To characterize the GNB1 gene further, we have cloned and analyzed the genomic structures of the mouse GNBI gene and its homologous sequences. The GNBI gene spans at least 50 kb, and consists of 12 exons and 11 introns. The exon/intron boundaries were determined and found to follow the GT/AG rule. Exons 3-11 encode the Gbeta1 protein, and the exon 2 is an alternative, resulting in putative two splicing variants. Although intron 11 is additional for GNBI compared with GNB2 and GNB3, the intron positions within the protein coding region of GNB1, GNB2 and GNB3 are identical, suggesting that GNB1 should have diverged from the ancestral gene family earlier than the genes for GNB2 and GNB3. We also found the 5'-truncated processed pseudogenes with 71-89% similarities to GNBI mRNA sequence, suggesting that the truncated cDNA copies, which have been reverse-transcribed from a processed mRNA for GNB1, might have been integrated into several new locations in the mouse genome.
异源三聚体鸟嘌呤核苷酸结合蛋白(G蛋白)在包括药物成瘾分子机制在内的许多生理过程中的功能意义已被描述。在研究急性精神兴奋剂给药后mRNA表达的变化时,我们之前鉴定出一个编码G蛋白β1亚基(Gβ1)的cDNA,在给予精神兴奋剂后,某些脑区中该cDNA增加了四倍。小鼠Gβ1基因(小鼠基因符号,GNB1)被定位到4号染色体,但对其遗传特征知之甚少。为了进一步表征GNB1基因,我们克隆并分析了小鼠GNBI基因及其同源序列的基因组结构。GNBI基因跨度至少50kb,由12个外显子和11个内含子组成。确定了外显子/内含子边界,发现其遵循GT/AG规则。外显子3至11编码Gβ1蛋白,外显子2是一个可变外显子,产生两个推定的剪接变体。尽管与GNB2和GNB3相比,GNBI的内含子11是额外的,但GNB1、GNB2和GNB3蛋白质编码区域内的内含子位置是相同的,这表明GNB1应该比GNB2和GNB3的基因更早地从祖先基因家族中分化出来。我们还发现了与GNBI mRNA序列具有71-89%相似性的5'-截短的加工假基因,这表明从GNB1的加工mRNA反向转录而来的截短cDNA拷贝可能已整合到小鼠基因组的几个新位置。