Abstract
Experimental work over the past several years has revealed an unexpected abundance of long natural antisense transcripts (NATs) in eukaryotic species. In light of the proposed role of such RNA molecules in the regulation of gene expression in the brain, attention is now focused on specific examples of neuronal NATs. Of particular interest are NATs that are complementary to mRNAs encoding nitric oxide synthase (NOS), the enzyme responsible for production of the important gaseous neurotransmitter nitric oxide (NO). Here we study the temporal expression profile of murine Nos3as NAT in the brain. Notably, Nos3as NAT is known to act as a negative regulator of Nos3 gene expression. The results of our quantitative analysis reveal differential expression of Nos3as NAT during embryonic and post-embryonic stages of development of the brain. Also, they show that the low levels of Nos3as NAT coincides with active neurogenesis. In addition we report on an inverse correlation between the relative expression level of Nos3as NAT and the level of Nos3 protein. Thus our data raise the hypothesis that the Nos3as NAT regulates neurogenesis through suppression of Nos3 gene activity. This idea is further supported by experiments conducted on the olfactory bulbs and cultured neuroblastoma cells.
Highlights
Long natural antisense transcripts (NATs) are endogenous RNA molecules that are complementary to RNA transcripts of already established function
To provide support for this hypothesis we investigated whether the observed changes in the relative expression level of Nos3as RNA are accompanied by alterations in Nos3 protein production
We found that the Nos3as RNA/Nos3 mRNA ratio is gradually increased over time after E15.5 (Fig. 2B)
Summary
Long natural antisense transcripts (NATs) are endogenous RNA molecules that are complementary to RNA transcripts of already established function. They are longer than 200 nt and depending on their origin can be classified as cis-encoded and trans-encoded NATs. Cisencoded NATs are produced from the same loci as their sense counterparts whereas trans-encoded NATs are transcribed from different loci. NO has been implicated in many physiological processes including the regulation of blood flow, neurotransmission, platelet aggregation and the immune response [8,9,10] It is produced by three major nitric oxide synthase (NOS) isoforms: neuronal NOS (NOS1), inducible NOS (NOS2) and endothelial NOS (NOS3). Taken together our data suggest that Nos3as RNA can be involved in the regulation of neurogenesis
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