Boissel J P, Schwarz P M, Förstermann U
Department of Pharmacology, Johannes Gutenberg University, Mainz, Germany.
Nitric Oxide. 1998;2(5):337-49. doi: 10.1006/niox.1998.0189.
Of the three established isoforms of NO synthase, the gene for the neuronal-type enzyme (NOS I) is by far the largest and most complicated one. The genomic locus of the human NOS I gene is located on chromosome 12 and distributed over a region greater than 200 kb. The nucleotide sequence corresponding to the major neuronal mRNA transcript is encoded by 29 exons. The full-length open reading frame codes for a protein of 1434 amino acids with a predicted molecular weight of 160.8 kDa. However, both in rodents and in humans, multiple, tissue-specific or developmentally regulated NOS I mRNA transcripts have been reported. They arise from the initiation by different transcriptional units containing alternative promoters (at least eight in the human gene), cassette exon deletions or insertions, and/or the usage of alternate polyadenylation signals. Depending on the insertions and deletions, translation results in functional or nonfunctional proteins. The use of alternative promoters can influence gene expression by various means. Indeed, NOS I is not a static, constitutively expressed enzyme, but subject to expressional regulation by various compounds and conditions. The molecular mechanisms underlying these regulations are currently being studied in several laboratories including our own.
在一氧化氮合酶的三种已确定的同工型中，神经元型酶（NOS I）的基因是迄今为止最大且最复杂的一个。人类NOS I基因的基因组位点位于12号染色体上，分布在超过200 kb的区域。对应主要神经元mRNA转录本的核苷酸序列由29个外显子编码。全长开放阅读框编码一个1434个氨基酸的蛋白质，预测分子量为160.8 kDa。然而，在啮齿动物和人类中，均已报道存在多种组织特异性或发育调控的NOS I mRNA转录本。它们源自不同转录单元的起始，这些转录单元包含替代启动子（人类基因中至少有八个）、盒式外显子缺失或插入，和/或使用替代聚腺苷酸化信号。根据插入和缺失情况，翻译会产生功能性或非功能性蛋白质。替代启动子的使用可通过多种方式影响基因表达。实际上，NOS I不是一种静态的、组成性表达的酶，而是受到各种化合物和条件的表达调控。包括我们自己实验室在内的几个实验室目前正在研究这些调控背后的分子机制。
