Talib S, Okarma T B, Lebkowski J S
Applied Immune Sciences, Inc., Menlo Park, CA 94025-1109.
Nucleic Acids Res. 1993 Jan 25;21(2):233-7. doi: 10.1093/nar/21.2.233.
The nicotinic acetylcholine receptor (nAChR) is an oligomeric transmembrane glycoprotein consisting of four homologous subunits in stoichiometry of alpha 2, beta (gamma or epsilon). Recently the presence of a novel exon (P3A) in human alpha AChR gene has been reported. Two variants of the human alpha subunit arise from alternate RNA splicing, one with and one without the P3A exon. However, the evolutionary origin of the P3A exon and the regulation of the expression of the two variants in human muscle and non-human tissues is currently unknown. Examination of genomic DNA from various species shows that the P3A exon sequence is present only in hominoids, old world and new world primates species and is absent in the muscle cDNA or genomic DNA from rat, mouse or dog, indicating that P3A exon is evolutionary conserved for at least 50 million years. The P3A+ variant of alpha subunit was found to be constitutively expressed in skeletal muscle, brain, heart, kidney, liver, lung and thymus, while P3A-variant was differentially expressed only in skeletal muscle. Thus it appears that the P3A+ variant is generated by 'default' selection by the splicing machinery, while expression of the P3A- variant is regulated by tissue-specific factors in the skeletal muscle. Mechanisms regulating differential expression of the alpha subunit variants may be pertinent to the pathophysiology of myasthenia gravis.
烟碱型乙酰胆碱受体（nAChR）是一种寡聚跨膜糖蛋白，由化学计量比为α2、β（γ或ε）的四个同源亚基组成。最近有报道称人类α-乙酰胆碱受体基因中存在一个新的外显子（P3A）。人类α亚基的两种变体源于交替的RNA剪接，一种含有P3A外显子，另一种不含。然而，P3A外显子的进化起源以及这两种变体在人类肌肉和非人类组织中的表达调控目前尚不清楚。对各种物种基因组DNA的检测表明，P3A外显子序列仅存在于类人猿、旧世界和新世界灵长类物种中，而在大鼠、小鼠或狗的肌肉cDNA或基因组DNA中不存在，这表明P3A外显子在至少5000万年的时间里一直保持进化保守。发现α亚基的P3A +变体在骨骼肌、脑、心脏、肾脏、肝脏、肺和胸腺中组成性表达，而P3A -变体仅在骨骼肌中差异表达。因此，似乎P3A +变体是由剪接机制通过“默认”选择产生的，而P3A -变体的表达则由骨骼肌中的组织特异性因子调节。调节α亚基变体差异表达的机制可能与重症肌无力的病理生理学相关。
