Nitric Oxide Receptor Soluble Guanylyl Cyclase Undergoes Splicing Regulation in Differentiating Human Embryonic Cells

Nitric oxide (NO), an important mediator molecule in mammalian physiology, initiates a number of signaling mechanisms by activating the enzyme soluble guanylyl cyclase (sGC). Recently, a new role for NO/cyclic guanosine monophosphate signaling in embryonic development and cell differentiation has emerged. The changes in expression of NO synthase isoforms and various sGC subunits has been demonstrated during human and mouse embryonic stem (ES) cells differentiation. Previously, our laboratory demonstrated that nascent alpha 1 sGC transcript undergoes alternative splicing and that expression of alpha 1 sGC splice forms directly affects sGC activity. Expression of sGC splice variants in the process of human ES (hES) cells differentiation has not been investigated. In this report, we demonstrate that alpha 1 sGC undergoes alternative splicing during random hES differentiation for the first time. Our results indicate that C-alpha 1 sGC splice form is expressed at high levels in differentiating cells and its intracellular distribution varies from canonical alpha 1 sGC subunit. Together, our data suggest that alternative splicing of sGC subunits is associated with differentiation of hES cells.