LMO4 mRNA stability is regulated by extracellular ATP in F11 cells.
LIM only domain protein 4 (LMO4) interacts with many signaling and transcription factors to regulate cellular proliferation, differentiation and plasticity. In Drosophila, mutations in the 3' untranslated region (UTR) of the homologue dLMO cause a gain of function by increasing mRNA stability. LMO4 3'UTR contains several AU-rich elements (ARE) and is highly conserved among vertebrates, suggesting that RNA destabilizing mechanisms are evolutionarily conserved. Here, we found that extracellular ATP stabilized LMO4 mRNA in F11 cells. The LMO4 3'UTR added to a luciferase reporter markedly reduced reporter activity under basal conditions, but increased activity with ATP treatment. Two ARE motifs were characterized in the LMO4 3'UTR. ATP increased binding of HuD protein to ARE1. ARE1 conferred ATP and HuD-dependent mRNA stabilization. In contrast, sequences flanking ARE2 bound CUGBP1 and ATP destabilized this complex. Thus, our results suggest that ATP modulates recruitment of RNA-binding proteins to the 3'UTR to stabilize LMO4 mRNA.
Chen
Hsiao-Huei
HH
Ottawa Health Research Institute, Neuroscience, Centre for Stroke Recovery, 451 Smyth Road, Ottawa, Ont., Canada K1H 8M5. hchen@uottawa.ca
Xu
Jin
J
Safarpour
Farzaneh
F
Stewart
Alexandre F R
AF
D048868:Adaptor Proteins, Signal Transducing; D000255:Adenosine Triphosphate / Q000008:administration & dosage* / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D045604:Extracellular Fluid / Q000378:metabolism; D018398:Homeodomain Proteins / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*; D060588:LIM Domain Proteins; D051379:Mice; D009474:Neurons / Q000502:physiology*; D020871:RNA Stability / Q000187:drug effects / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D014157:Transcription Factors / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D018398:Homeodomain Proteins; D060588:LIM Domain Proteins; C491976:Lmo4 protein, mouse; D012333:RNA, Messenger; D014157:Transcription Factors; D000255:Adenosine Triphosphate