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 α1 sGC transcript undergoes alternative splicing and that expression of α1 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 α1 sGC undergoes alternative splicing during random hES differentiation for the first time. Our results indicate that C-α1 sGC splice form is expressed at high levels in differentiating cells and its intracellular distribution varies from canonical α1 sGC subunit. Together, our data suggest that alternative splicing of sGC subunits is associated with differentiation of hES cells.
UT Health Science Center, Brown Foundation Institute of Molecular Medicine, Houston, Texas, USA.
Vladislav G
VG
Sharin
Kalpana
K
Mujoo
Alexander Y
AY
Kots
Emil
E
Martin
Ferid
F
Murad
Iraida G
IG
Sharina
D017398:Alternative Splicing; D015153:Blotting, Western; D002454:Cell Differentiation; D002460:Cell Line; D006152:Cyclic GMP / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D006162:Guanylate Cyclase / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000378:metabolism; D000071317:Nanog Homeobox Protein; D009569:Nitric Oxide / Q000378:metabolism; D050814:Octamer Transcription Factor-3 / Q000378:metabolism; D027701:Organic Cation Transport Proteins / Q000378:metabolism; D018384:Oxidative Stress; D020033:Protein Isoforms / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D000071756:Soluble Guanylyl Cyclase; D000099254:Organic Cation Transporter 3
D006152:Cyclic GMP; D006162:Guanylate Cyclase; D018398:Homeodomain Proteins; D007527:Isoenzymes; D000071317:Nanog Homeobox Protein; D009569:Nitric Oxide; D050814:Octamer Transcription Factor-3; D027701:Organic Cation Transport Proteins; D020033:Protein Isoforms; D018160:Receptors, Cytoplasmic and Nuclear; D000071756:Soluble Guanylyl Cyclase; D000099254:Organic Cation Transporter 3; C486780:NANOG protein, human; C494173:POU5F1 protein, human