Sussex Neuroscience, School of Life Science, University of Sussex, Brighton, BN1 9QG, UK.
Sussex Neuroscience, School of Life Science, University of Sussex, Brighton, BN1 9QG, UK.
Nitric Oxide. 2017 Dec 1;71:27-31. doi: 10.1016/j.niox.2017.10.002. Epub 2017 Oct 12.
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.
在过去的几年中，实验工作揭示了真核生物中存在大量出人意料的长自然反义转录本 (NAT)。鉴于这些 RNA 分子在大脑基因表达调控中的作用，人们现在将注意力集中在特定的神经元 NAT 上。特别引人注目的是与编码一氧化氮合酶 (NOS) 的 mRNA 互补的 NAT，NOS 是产生重要气体神经递质一氧化氮 (NO) 的酶。在这里，我们研究了脑中小鼠 Nos3as NAT 的时间表达谱。值得注意的是，已知 Nos3as NAT 作为 Nos3 基因表达的负调节剂。我们的定量分析结果揭示了 Nos3as NAT 在大脑胚胎和胚胎后发育阶段的差异表达。此外，它们表明 Nos3as NAT 的低水平与活跃的神经发生相一致。此外，我们还报告了 Nos3as NAT 的相对表达水平与 Nos3 蛋白水平之间的反比相关性。因此，我们的数据提出了这样一种假设，即 Nos3as NAT 通过抑制 Nos3 基因活性来调节神经发生。这个想法进一步得到了在嗅球和培养的神经母细胞瘤细胞上进行的实验的支持。
