Neuronal-type NO Synthase: Transcript Diversity and Expressional Regulation

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.