RNA splicing in regulation of nitric oxide receptor soluble guanylyl cyclase.
RNA splicing in regulation of nitric oxide receptor soluble guanylyl cyclase.
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DOI：
10.1016/j.niox.2011.08.001
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发表时间：
2011-10-30
期刊：
影响因子：
--
通讯作者：
Murad F
中科院分区：
文献类型：
--
作者：
Sharina IG;Cote GJ;Martin E;Doursout MF;Murad F
可溶性鸟苷酸环化酶 (sGC) 是一氧化氮 (NO)/-cGMP 信号通路中的关键蛋白。 sGC 活性参与许多重要的生理过程，包括平滑肌松弛、神经传递以及血小板聚集和粘附。 sGC 表达和活性的调节成为正常和病理条件下控制 sGC 功能的关键因素。最近积累的证据有力地表明，sGC 表达的调节是一个在多个水平上进行调节的复杂过程，包括转录、转录后调节、翻译和蛋白质稳定性。目前，我们对 sGC 表达调控机制的理解仍然非常有限，有待系统研究。除其他方式外，sGC 亚基的表达在 mRNA 丰度和转录多样性水平上受到调节。在这篇综述中，我们总结了有关 sGC 亚基 mRNA 水平调节以响应各种环境线索的不同机制（包括转录激活、mRNA 稳定性和选择性剪接）的现有信息。我们还总结并交叉引用了文献和基因组数据库中有关人类 sGC 剪接形式的信息。这篇综述强调了这样一个事实：对 sGC 剪接的生物学作用和调控的研究将为我们对 NO/cGMP 生物学的理解带来新的见解。
Soluble guanylyl cyclase (sGC) is a key protein in the nitric oxide (NO)/-cGMP signaling pathway. sGC activity is involved in a number of important physiological processes including smooth muscle relaxation, neurotransmission and platelet aggregation and adhesion. Regulation of sGC expression and activity emerges as a crucial factor in control of sGC function in normal and pathological conditions. Recently accumulated evidence strongly indicates that the regulation of sGC expression is a complex process modulated on several levels including transcription, post-transcriptional regulation, translation and protein stability. Presently our understanding of mechanisms governing regulation of sGC expression remains very limited and awaits systematic investigation. Among other ways, the expression of sGC subunits is modulated at the levels of mRNA abundance and transcript diversity. In this review we summarize available information on different mechanisms (including transcriptional activation, mRNA stability and alternative splicing) involved in the modulation of mRNA levels of sGC subunits in response to various environmental clues. We also summarize and cross-reference the information on human sGC splice forms available in the literature and in genomic databases. This review highlights the fact that the study of the biological role and regulation of sGC splicing will bring new insights to our understanding of NO/cGMP biology.
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